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PubMed1992

Collagen synthesis in fibroblasts from human colon: regulatory aspects and differences with skin fibroblasts.

The purpose of this study was to examine regulation of collagen synthesis in human colon fibroblasts and compare the results from colon fibroblasts with those obtained in fibroblasts from human skin. The effects of interleukin-1 beta, tumour necrosis factor alpha, interferon gamma, transforming growth factor-beta, dexamethasone, and the calcium ionophore A23187 were investigated. All compounds were tested both in the absence and in the presence of fetal calf serum in the culture medium. The process of collagen synthesis in fibroblasts from colon and skin appears to be affected differently by these regulatory compounds. The most pronounced differences were that the relative collagen synthesis increased in dermal fibroblasts and decreased in colon fibroblasts upon addition of serum. In the presence of serum, interleukin-1 beta inhibited collagen synthesis in skin fibroblasts but not in colon fibroblasts. Dexamethasone suppressed the relative collagen synthesis in skin fibroblasts but not in colon fibroblasts. Transforming growth factor-beta stimulated the collagen synthesis in dermal fibroblasts in the presence of serum, but inhibited the process in colon fibroblasts. Because fibroblasts are the primary sources of collagen needed during wound repair, these results may offer (part of) the explanation why wounds in skin and intestine appear to behave differently under certain conditions.

Calcimycin↗
PubMed2002

Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes.

The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations that could explain regional variation in epithelial growth and wound healing. Normal human fibroblasts were cultured on polystyrene or maintained in collagen matrix and stimulated with keratinocytes cultured on membranes. The amount of HGF and KGF protein in the culture medium was determined every 24 h for 5 days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When cells were maintained in collagen, the level of HGF and KGF was decreased mainly in skin cultures. However, in oral fibroblasts, induction after stimulation was at a similar level in collagen compared to on polystyrene. Skin fibroblasts maintained in collagen produced almost no HGF whether with or without stimulation. The results demonstrate that the secretion of KGF and HGF in both unstimulated fibroblasts and in fibroblasts co-cultured with keratinocytes is dependent on the type of fibroblasts. In general, the periodontal fibroblasts had the highest level of cytokine production. This high level of growth factor production may influence the proliferation and the migration of junctional epithelium and thereby influence the development of periodontal disease.

Cell Division↗
PubMed1996

Heterogeneity of collagen synthesis in normal and systemic sclerosis skin fibroblasts. Increased proportion of high collagen-producing cells in systemic sclerosis fibroblasts.

OBJECTIVE: The goal of this study was to quantitatively analyze the distribution of collagen synthesis in normal and systemic sclerosis (SSc) fibroblast populations in order to determine the extent of activation in SSc populations. METHODS: We used quantitative in situ hybridization to assess the population distribution of type I collagen synthesis. Fibroblast cultures were derived from both clinically involved and uninvolved skin regions of patients with SSc, and from healthy adults, and assessed for levels of alpha 1(I) procollagen messenger RNA (mRNA). RESULTS: Dermal fibroblasts from both patients with SSc and normal adults were heterogeneous for distribution of alpha 1(I) procollagen mRNA when assessed by in situ hybridization, with a wide range of grains per cell. In contrast, clones of neonatal fibroblasts showed a relatively homogeneous distribution of grain counts. Involved SSc skin fibroblasts had a larger proportion of cells in the high collagen-producing mRNA subpopulation (mean +/- SEM 28.4 +/- 6.85%), compared with normal fibroblasts (1.75 +/- 1.44%) and uninvolved fibroblasts (9.6 +/- 6.73%). Conversely, within the low collagen-producing mRNA subpopulation, involved fibroblasts had a smaller proportion of cells (mean +/- SEM 14.0 +/- 5.63%) than did uninvolved fibroblasts (37.8 +/- 13.69%), while normal fibroblasts had a majority of the cells in this subpopulation (53.5 +/- 8.68%). CONCLUSION: These results suggest that only a specific subset of fibroblasts are activated in SSc, as evidence by an increased proportion of cells with high levels of alpha 1(I) procollagen mRNA. Differences between the SSc and normal fibroblast populations appeared to be quantitative rather than qualitative. This may be a result of either clonal selection or selective activation in the pathogenesis of SSc.

Adult↗
PubMed1994

Phenotypic heterogeneity in breast fibroblasts: functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma.

Histologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (1 non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.

Adipose Tissue↗
PubMed1994

Human wound healing fibroblasts have greater contractile properties than dermal fibroblasts.

Contractile and phenotypic properties of human fibroblasts from healing wounds were compared to those of dermal fibroblasts using in vitro models. Wound fibroblasts were recovered from implants, made of a polyvinyl alcohol sponge threaded into a perforated silicone tube, 12 days after their subcutaneous implantation in human volunteers. Dermal fibroblasts were isolated from the skin of healthy subjects. Two morphologically different fibroblast populations were observed in cells cultured from implants. In order to characterize these fibroblast populations, intracellular alpha-actin expression was studied by immunofluorescence labeling of cells cultured in monolayer. This protein was detected in less than 1% of the dermal fibroblasts. By contrast, 30 to 40% of wound fibroblasts were labeled and contained fiber networks of alpha-actin. These results confirm the presence of myofibroblasts in human wound healing tissues. The contractile property of fibroblasts and myofibroblasts was evaluated using a three-dimensional cell culture model (fibroblast populated collagen gels). Cells were incorporated in a collagen matrix and cultured for 14 days. The surface area of collagen gels was measured every day. Our results show that wound fibroblasts strongly contract collagen gels during the first 24 hr (surface area at 24 hr = 20-55% of initial surface area) in comparison to dermal fibroblasts (surface area at 24 hr = 70-75% of initial surface area). This superior level of contraction was observed until the fifth day of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed2000

Rapid gene transcription induced by stretch in cardiac myocytes and fibroblasts and their paracrine influence on stationary myocytes and fibroblasts.

Functional adaptation of cardiac cells in response to haemodynamic load requires dynamic alteration of gene expression. In this study, we examined early changes in gene expression following stretch in myocytes and fibroblasts isolated from neonatal rat hearts. In the first hour of biaxially applied static stretch, the changes in expression of immediate-early genes, such as c-fos, c-jun and fra-1, were quantified. The expression of the atrial natriuretic peptide (ANP) gene in myocytes was measured as an indication of the hypertrophic response. In stretched myocytes, expression of c-fos and ANP increased transiently to 227% and 176% respectively after 30 min stretch, whereas c-jun and fra-1 expression decreased in the 1st hour of stretch. In stretched fibroblasts the expression of c-fos and fra-1 increased transiently to maxima of 145% and 146% respectively after 30 min stretch, whereas c-jun expression did not change significantly. To study the indirect effects of stretch, as an indication of cross-talk between cardiac cells, stationary myocytes and fibroblasts were incubated with stretch-conditioned medium (CM) from stretched (0-60 min) myocytes and fibroblasts. CM from stretched myocytes reduced c-fos and induced c-jun expression in myocytes and fibroblasts, reduced fra-1 expression in myocytes but induced fra-1 expression in fibroblasts. CM from stretched fibroblasts induced c-fos expression and had little effect on c-jun expression in myocytes and fibroblasts, induced the fra-1 expression in myocytes but had little effect on fra-1 expression in fibroblasts. CM from myocytes and CM from fibroblasts induced ANP expression in myocytes to 206% and 120% respectively after 45 min stretch. Static stretch of myocytes and fibroblasts appears to stimulate, within 1 h, secretion of cell type-specific factors that participate in the regulation of proto-oncogene and ANP expression of stationary myocytes and fibroblasts. These early changes in gene transcription suggest that stretch of the myocardium initiates intracellular gene expression as well as cross-talk between the cell types.

Animals↗
PubMed1983

Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.

Bleomycin-induced pulmonary fibrosis in hamsters is associated with collagen accumulation that results from increased lung collagen synthesis rates. However, 1-2 wk after intratracheal instillation of bleomycin, lung collagen synthesis rates decline toward control values. To evaluate the potential role of the bronchoalveolar macrophage in regulating lung collagen production, we studied the effects of macrophages from normal and bleomycin-treated hamsters upon fibroblasts in vitro. We observed: (a) Medium from macrophage cultures decreased fibroblast [3H]thymidine incorporation and nondialyzable [3H]hydroxyproline production in a dose-dependent manner. Fibroblast cell counts were decreased in exposed cultures, and fibroblast viability was unchanged. Procollagen prolyl hydroxylation and prolyl-transfer RNA-specific activity were not altered by macrophage medium; this indicates that [3H]hydroxyproline reflects collagen production rate under the experimental conditions. (b) The suppressive effect of macrophage medium was selective for collagen since collagen production decreased more than noncollagen protein production. (c) Medium from bleomycin-treated hamster macrophages suppressed fibroblast proliferation and collagen production to a greater degree than medium from normal hamster macrophages. (d) Fibroblast suppression by macrophage medium was associated with increased fibroblast endogenous prostaglandin E2 production and intracellular cyclic AMP (cAMP). (e) Incubation of fibroblasts with indomethacin before exposure completely inhibited prostaglandin E2 production and increases in cAMP, and eliminated suppression of fibroblast proliferation and collagen production. The macrophage-derived suppressive factor has an apparent molecular weight of 20,000-30,000 and is heat stable. It does not appear to be species restricted since both hamster and human lung fibroblasts are similarly suppressed. It is at least in part preformed in macrophages obtained by lavage, but its production can also be stimulated in vitro. We concluded that alveolar macrophages release a product that stimulates endogenous fibroblast prostaglandin E2 production and cAMP formation with resultant suppression of fibroblast proliferation and collagen production. Enhanced release of suppressive factor by macrophages during a time when lung collagen production is declining in bleomycin-induced pulmonary fibrosis suggests that macrophages may limit collagen accumulation in pulmonary fibrosis.

Animals↗
PubMed1980

[A study of the effect of dihydrotestosterone on cultured human fibroblasts--with special reference to the hormone effect on the synthesis of proteins, collagen and DNA in fibroblasts (author's transl)].

Fibroblasts grown from abdominal and vulvar skin from normal women were tested for their dihydrotestosterone binding activity. Fibroblasts from either source had 8S cytoplasmic dihydrotestosterone receptors as confirmed by sucrose gradient analysis and the concentration of dihydrotestosterone binding sites and the apparent dissociation constant were 21.6 +/- 1.1 fmoles/mg protein and 0.50 +/- 0.028 nM, respectively, for fibroblasts from abdominal skin and 35.9 +/- 1.7 fmoles/mg protein and 0.24 +/- 0.015 nM, respectively, for fibroblasts from vulvar skin. The dihydrotestosterone binding activity was greater in fibroblasts from vulvar skin than from abdominal skin (P less than 0.01). Fibroblasts formed dense monolayers were treated with various concentrations of dihydrotestosterone (10, 100, 1,000 ng/ml) for six days and were assessed for hormone effect. The production of proteins was elevated in fibroblasts from either source with a slightly greater hormonal response occurring in fibroblasts from vulvar skin than from abdominal skin. Collagen production was elevated significantly in fibroblasts from vulvar skin but only marginally in fibroblasts from abdominal skin. The synthesis of DNA was not affected in fibroblasts from either source. These results than response to dihydrotestosterone was greater in fibroblasts with a higher hormone binding activity may reflect the hormone effect being mediated through dihydrotestosterone receptors.

Cells, Cultured↗
PubMed1996

Differential in vitro responses of elastin expression to basic fibroblast growth factor and transforming growth factor beta 1 in upper, middle and lower dermal fibroblasts.

Elastin mRNA levels were measured in cultured skin fibroblasts derived from upper, middle and lower dermal layers. The elastin mRNA levels were highest in the fibroblasts from the upper dermal layer and lowest in the lower dermal fibroblasts. Modulation of elastin expression by basic fibroblast growth factor and transforming growth factor beta 1 in the dermal fibroblasts was also studied. Basic fibroblasts growth factor downregulated elasin expression in the upper dermal fibroblasts but did not significantly change elastin expression in the middle and lower dermal fibroblasts. Upregulation of elastin expression by transforming growth factor beta 1 was greater in the upper dermal fibroblasts than in the middle and lower dermal fibroblasts. Platelet-derived growth factor induced no significant changes in the three types of dermal fibroblasts. The results suggest that the differential responses of elastin expression to potent modulators may be at least partially responsible for the abnormal elastin metabolism specifically observed in the upper dermal layer.

Adult↗
PubMed1995

Different effects of basic fibroblast growth factor and transforming growth factor-beta on the two platelet-derived growth factor receptors' expression in scleroderma and healthy human dermal fibroblasts.

Previous studies have demonstrated that platelet-derived growth factor (PDGF) alpha receptor expression is up-regulated by transforming growth factor-beta 1 (TGF-beta 1) in scleroderma dermal fibroblasts, but not in healthy control fibroblasts. We asked whether this selective effect in scleroderma cells was TGF-beta 1-specific or a general response by studying responses to other growth factors. In this study, we compared the expression of alpha and beta PDGF receptor subunits (mRNA and protein levels) in these two cell types in response to basic fibroblast growth factor (bFGF) and TGF-beta 1. bFGF coordinately stimulated mRNA levels of alpha and beta receptor subunits in healthy fibroblasts, but did not change PDGF receptor expression in scleroderma fibroblasts. Conversely, and in agreement with previous observations, TGF-beta 1 induced PDGF alpha receptor expression in scleroderma fibroblasts, but not in healthy fibroblasts. PDGF beta receptor mRNA levels were induced to similar degrees by TGF-beta 1 in both cell types. PDGF alpha receptor protein levels correlated directly with mRNA levels, induced by bFGF only in healthy fibroblasts and by TGF-beta 1 only in scleroderma fibroblasts. However, PDGF beta receptor protein levels were not altered by either growth factor in either cell type. Thus, the activated state of scleroderma fibroblasts does not include receptor-signaling pathways to bFGF. This distinct pattern of expression of PDGF alpha receptors in scleroderma fibroblasts suggests a possible role for the coordinately expressed PDGF AA ligand/alpha receptor system in the development of fibrosis.

Blotting, Western↗
PubMed2002

Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis.

OBJECTIVE: Fibroblasts play a major role in the development of systemic sclerosis (SSc), and the occurrence of serum autoantibodies reacting with fibroblast plasma membrane antigens in SSc has been reported. This study was undertaken to investigate whether IgG from SSc sera that react with human fibroblasts modulates the fibroblasts' function. METHODS: Sera from 69 patients with SSc (28 with limited cutaneous SSc [lcSSc] and 41 with diffuse cutaneous SSc [dcSSc]), 30 patients with sarcoidosis, and 50 matched healthy controls were examined. We evaluated antibody binding to human skin and lung fibroblasts by cell-based enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence, and flow cytometry. We further investigated the ability of purified IgG to modulate 1) intercellular adhesion molecule 1 (ICAM-1) expression, 2) U937 cell adhesion to fibroblasts, and 3) fibroblast steady-state messenger RNA (mRNA) levels of interleukin-1alpha (IL-1alpha), IL-beta, and IL-6, and IL-6 protein production. RESULTS: Of 69 SSc sera tested by cell-based ELISA, 58% bound to normal skin and lung fibroblasts. The prevalence of binding was significantly higher in dcSSc than in lcSSc (P < 0.05). Only IgG from SSc sera that were positive for antifibroblast antibody (AFA) induced a dose-dependent up-regulation of ICAM-1 expression and IL-6 production, enhancement of U937 cell adhesion, and increased levels of IL-1alpha, IL-1beta, and IL-6 mRNA in fibroblasts. Up-regulation of ICAM-1 mediated by AFA IgG was inhibited by the addition of IL-1 receptor antagonist, indicating an autocrine activation loop. CONCLUSION: Our findings confirm the presence of AFAs in SSc sera and demonstrate, for the first time, that autoantibodies reacting with fibroblast surface molecules act as an extrinsic stimulus inducing fibroblast activation in vitro.

Adult↗
PubMed1985

Monocyte inhibition of lung fibroblast growth: relationship to fibroblast prostaglandin production and density-defined monocyte subpopulations.

Mononuclear cell fibroblast interactions in the normal human lung are poorly understood. Mononuclear cells can regulate fibroblast function and blood monocytes are known to migrate to the lung and participate in pulmonary inflammation. Thus, to clarify mononuclear cell-fibroblast interactions in the normal lung, we obtained supernatants from adherent monocytes and characterized their effect on the log phase growth of human lung fibroblasts. Monocyte supernatants inhibited fibroblast growth in a dose-dependent fashion. The inhibition was the result of an approximately 16,000 MW soluble factor(s) that was heat stable, trypsin sensitive, and chymotrypsin resistant. Elaboration of the factor(s) required monocyte protein synthesis and was not restricted to a density-defined monocyte subpopulation. The inhibitory capacity of a monocyte supernatant was directly related to its ability to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by monocyte supernatants. Thus, monocyte inhibition of fibroblast growth may be mediated by fibroblast prostaglandin production. Recruitment of monocytes to the lung and subsequent monocyte inhibition of fibroblast growth may be important in regulating pulmonary fibrosis.

Cell Division↗
PubMed1990

Re-evaluation of fibroblasts and fibroblast-like cells.

Scanning electron microscopic observations of connective tissue cells show a new aspect of the nature of fibroblasts, and the subsequent broad survey of references makes clear that fibroblasts of many tissues have various features which are regarded as atypical of fibroblasts, and at the same time that various connective tissue cells in different organs have features typical of fibroblasts. Both morphological and functional features of fibroblasts are more or less common to those of fibroblast-like cells, and differences among these cells are quantitative rather than qualitative. Therefore, it is almost impossible to set clear-cut criteria for distinguishing genuine fibroblasts from a large population of fibroblast-like cells. The majority of cells sharing features of fibroblasts, if not all, seem to belong to the same population of cells. They are probably adapted to special functional needs in their own micro-environment that are peculiar to local or pathological or experimental conditions. It is proposed to categorize these cells into subtypes depending on their main functions: 1, fibrogenesis; 2, tissue skeleton or barrier; 3, intercellular communication system; 4, gentle contractile machinery; 5, endocrine activity; and 6, vitamin A-storing. Re-evaluation of fibroblasts and fibroblast-like cells is required to facilitate their better understanding.

Animals↗
PubMed1996

Coordinate suppression of myeloma-specific genes and expression of fibroblast-specific genes in myeloma X fibroblast somatic cell hybrids.

In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of the differentiation-specific traits of the non-fibroblast parental cell. To explore the genetic basis of this phenomenon, we have studied a series of somatic cell hybrids between mouse myeloma and fibroblasts. All the hybrids were adherent having a fibroblast-like phenotype. Molecular analysis revealed that plasma cell specific genes like the productively rearranged Ig genes, the J chain gene and genes for the cell surface markers CD20 and PC1, were extinguished in the hybrids. In contrast, fibroblast specific genes like fibronectin, alpha 2(I) and III collagens, as well as the receptor for fibroblast growth factor (flg), were expressed. Extinction was not due to chromosomal loss or lack of the relevant genes. To learn about the mechanism(s) of this phenomenon we have looked for the presence of positive and negative transcription factors in our hybrids. Expression of the PU.1 transcription factor, a member of the Ets transcription factor family normally expressed in B cells and macrophages, was lost in the cell hybrids. Interestingly, we found that the B-cell-specific Oct-2 transcription factor was still expressed at somewhat variable levels in several of the hybrid cell lines. In contrast, expression of the recently identified octamer coactivator BOB.1/OBF.1 was extinguished in all cell hybrids. This supports a critical role of this transcriptional coactivator for B-cell-specific gene expression. In addition, the Id and HLH462 genes coding for proteins known to repress bHLH transcription factors by formation of heterodimers, were found to be expressed at increased levels in fibroblasts and in the hybrids, indicating that their increased levels might also contribute to the suppression of myeloma-specific genes. Our results show that in myeloma x fibroblast hybrids, the phenotype of the fibroblast is dominant. It is suggested that fibroblasts contain regulatory "master" genes that are responsible for activation of the fibroblast differentiation pathway and suppress differentiation programs of other cell types.

Animals↗
PubMed1994

Activation of fibroblast proliferation by Werner's syndrome fibroblast-conditioned medium.

The effects of Werner's syndrome (WS) fibroblast-conditioned medium on cell proliferation and collagen production of normal fibroblasts were studied using four WS fibroblast strains. The conditioned medium from the WS fibroblasts brought about activation of normal fibroblast proliferation, whereas, that from late passage normal fibroblasts and fibroblasts from aged donors' skin did not. Collagen and non-collagenous protein synthesis in normal fibroblasts were increased by the addition of conditioned medium from the WS fibroblasts, but the relative rates of collagen synthesis and non-collagenous protein synthesis were unaltered. These results suggest that activation of fibroblast proliferation by conditioned medium is one of the characteristics of WS fibroblasts.

Adult↗
PubMedDate not supplied

Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts.

Abdominal wall fascial wound healing failure is a common clinical problem for general surgeons, manifesting in early postoperative fascial dehiscence as well as delayed development of incisional hernias. We previously reported that abdominal wall fascial incisions normally recover breaking strength faster than simultaneous dermal incisions in a rodent model. The accelerated fascial repair was associated with greater fibroblast cellularity within fascial wounds and increased wound collagen deposition. The current study was designed to determine whether accelerated fascial healing is the result of increased fascial fibroblast kinetic activity as measured by a more efficient fibroblast phenotype for binding to and remodeling a collagen matrix. Using a new model of abdominal wall repair, fibroblast cell cultures were developed from uninjured and wounded fascia and compared to dermal fibroblasts in order to define the fibroproliferative kinetic properties of abdominal wall fibroblasts. Fascial wound fibroblasts produced a more efficient and greater overall collagen lattice compaction compared to dermal fibroblasts. Acute fascial wound fibroblasts also showed enhanced cell proliferation compared to dermal fibroblasts but no significant differences in collagen production when normalized to cell number. These results suggest that fascial fibroblasts express distinct acute repair phenotypes and therefore a specific mechanism for fascial repair following injury.

Abdominal Wall↗
PubMed1998

Continuity between wound macrophage and fibroblast phenotype: analysis of wound fibroblast phagocytosis.

Analysis of phagocytic activity in wound fibroblasts was chosen as a means to assess the possible continuity between macrophage and fibroblast phenotypes. Fibroblast phagocytosis of uncoated, IgG-coated, or collagen-coated fluorescent beads was analyzed by flow cytometry in vivo and in vitro. Phagocytosis of fluorescent beads by procollagen I-positive cells (fibroblasts) was evaluated in vivo by injecting beads into subcutaneously implanted sponge wounds in anesthetized Fisher rats. Phagocytic activity of a purified population of wound fibroblasts was measured in vitro and correlated with oxidation state using hydroethidium. In the wound environment, 50-60% of the cells that engulfed uncoated, IgG-coated, or collagen-coated beads were procollagen I-positive cells (i.e., fibroblasts). Procollagen I-positive cells engulfed uncoated and IgG-coated beads in preference to collagen-coated beads in vivo. Cultured wound fibroblasts engulfed uncoated, IgG-coated, and collagen-coated particles. The majority of fibroblasts that engulfed beads were in an elevated oxidation state. We conclude that substantial fibroblast phagocytosis occurs in the wound, but scavenger receptor-mediated fibroblast phagocytosis is different from that of macrophages. Additional markers will be helpful in defining the macrophage fibroblast continuum.

Animals↗
PubMed1988

Tumor necrosis factor interacts with interleukin-1 and interferons to inhibit fibroblast proliferation via fibroblast prostaglandin-dependent and -independent mechanisms.

Mononuclear cells are important regulators of fibroblast function. However, the soluble factors mediating these effects and the importance of intercytokine interactions in these regulating events remain poorly understood. We analyzed the effect of recombinant (r) interleukin-1-alpha (IL-1), tumor necrosis factor (TNF), and gamma, alpha, and beta 1 interferons (IFN), alone and in combination, on the proliferation of normal human lung fibroblasts. rIL-1 and rTNF weakly stimulated and the rIFNs inhibited fibroblast proliferation. Importantly, when rTNF was combined with rIL-1 or rIFN, synergistic inhibition of fibroblast proliferation was noted. The inhibition caused by rIFN-gamma plus rTNF was largely independent of fibroblast prostaglandin (PG) production because fibroblast PG levels were unaltered in the presence of these cytokines and blocking fibroblast PG production did not alter their inhibitory effect. In contrast, the inhibition caused by rIL-1 plus rTNF appeared to be at least partially mediated by fibroblast PG production because these cytokines acted synergistically to stimulate fibroblast PG production and blocking fibroblast PG production reversed the inhibition that they caused. These studies demonstrate that TNF can interact with IL-1 or IFN to inhibit the proliferation of normal diploid fibroblasts and that the inhibitory effects of these cytokine combinations are mediated by different mechanisms.

Cell Division↗