Biomedical subjects

D J Romberger

Publications and source records attributed to D J Romberger.

At least 19 recordsLinked to original sources

PubMed2000

Effects of interferons alpha and gamma on cytokine production and phenotypic pattern of human bronchial epithelial cells.

Human bronchial epithelial cells are involved in airway immune mechanisms through secretion of cytokines and through cell-cell contacts with immunocompetent cells. The aim of our study was to assess the ability of interferon (IFN) alpha and gamma alone and in combination to modulate human bronchial epithelial cell (HBECs) release of the inflammatory cytokines IL-8 and IL-6 and fibronectin and to induce the surface expression of HLA-DR and ICAM-1 molecules involved in immune interactions with other cells. HBECs spontaneously secreted a limited amount of IL-8, which was significantly increased by IFN gamma. IFN alpha inhibited IFN gamma stimulated IL-8 secretion in a concentration-dependent manner. Further, IFN gamma induced IL-6 and fibronectin secretion, and this was also inhibited by IFN alpha. The expression of HLA-DR antigens was significantly increased by IFN gamma and partially inhibited by co-stimulation with IFN alpha. In contrast, IFN gamma also induced ICAM-1 expression by HBECs but co-stimulation with IFN alpha had no significant effect on the expression of this surface antigen. IFN alpha modulation of HBEC functions does not seem to be restricted to IFN gamma stimulation since either stimulatory or inhibitory effects of INF alpha on IL-8 production have been found in pilot experiments using IL-1 beta, TNF alpha, and TGF beta as stimuli. In summary, IFN-gamma induces a number of responses in HBECs including increased secretion of IL-6, IL-8 and fibronectin and increased expression of HLA-DR and ICAM-1. IFN alpha can inhibit all these except expression of ICAM-1 which is unaffected. IFN alpha can also interact with other inflammatory cytokines, but whether the effects are inhibitory or augmentive depends on the cytokines.

Bronchi↗

PubMed2000

Host defenses and pathogenesis.

The lung is protected by an array of interacting defense mechanisms.These include mechanical defenses that filter and remove particulates from the inhaled air as well as mechanisms to capture and remove particulates that penetrate into the lung as well as chemical and cellular defenses that can kill invading microorganisms. Optimal lung defense requires coordinated action of these various defenses. However, whereas failure of any defense mechanism increases the risk of infection, the various mechanisms provide, at least to a certain extent, redundant protection. As a result, many individuals with compromise of a single defense mechanism may not become clinically ill. Syndromes characterized by chronic infection of the lower respiratory tract are therefore associated with several defects in respiratory tract defense.

Apoptosis↗

PubMed2000

Endothelial cell-mediated type I collagen gel contraction is regulated by hemin.

The contraction of three-dimensional type I collagen gels is regarded as a model of contraction during wound healing and tissue remodeling. Because such a process could contribute to vessel narrowing, we hypothesized that endothelial cells may be able to mediate gel contraction. To demonstrate this, type I collagen was extracted from rat tail tendon and used to prepare collagen gels. Bovine arterial endothelial cells (BAECs) or human pulmonary artery endothelial cells (HPAECs) were then plated on the top of the gels in serum-free Ham's F-12 medium or 2% fetal calf serum-endothelium growth medium-2 (FCS-EGM2), respectively. After 48 hours of attachment, gels were released and floated in 0.2% FCS-Ham's F-12 medium (BAECs) or 2% FCS-EGM2 (HPAECs). Gel size was measured with an image analyzer daily for 5 consecutive days. Gels were then digested with collagenase to quantify DNA and hydroxyproline. BAECs contracted the gels in a time-dependent manner over the 5 days. Contraction was dependent on cell density (gel size was 100% of initial size after 5 days with no cells vs. 66.4%+/-0.5% with 0.9x10(4) cells/cm2 and 22.1%+/-0.3% with 7.5x10(4) cells/cm2) and was inversely related to collagen concentration (gel size was 22.3%+/-0.05%, 46.4%+/-0.9%, 72.3%+/-0.4%, and 87.4% +/-0.3% of initial size for gels prepared with 0.5 mg/mL, 0.75 mg/mL, 1 mg/mL, and 2 mg/mL of collagen, respectively). Hemin (a precursor for CO) and cytochalasin D inhibited collagen gel contraction mediated by both bovine and human endothelial cells without changing cell number or hydroxyproline content. In contrast, prostaglandin E2, an inhibitor, and transforming growth factor-beta1, a stimulator of fibroblast-mediated gel contraction, had no effect on endothelial cell-mediated contraction. These findings demonstrate that endothelial cells are able to contract native type I collagen gels and that this process can be modulated by exogenous mediators. Such a capability may cause remodeling of subjacent matrix of endothelial cells and may contribute to vessel narrowing.

Animals↗

PubMed2000

beta-Adrenergic agonist modulation of monocyte adhesion to airway epithelial cells in vitro.

beta-Adrenergic agonists are commonly used in the treatment of obstructive airway diseases and are known to modulate cAMP-dependent processes of airway epithelial cells. However, little is known regarding the ability of cAMP-dependent mechanisms to influence cell-cell interactions within the airway. Thus we investigated the role of the beta-adrenergic agonist isoproterenol in modulating the ability of human bronchial epithelial cells to support the adhesion of THP-1 cells, a monocyte/macrophage cell line, in vitro. We demonstrated that pretreatment of human bronchial epithelial cells (HBECs) with 10 microM isoproterenol or 100 microM salbutamol augments the adhesion of fluorescently labeled THP-1 cells to HBEC monolayers by approximately 40-60%. The increase in THP-1 cell adhesion occurred with 10 min of isoproterenol pretreatment of HBECs and gradually declined but persisted with up to 24 h of isoproterenol exposure. Exposure of THP-1 cells to isoproterenol or salbutamol before the adhesion assays did not result in an increase in adhesion to HBECs, suggesting that the isoproterenol modulation was primarily via changes in epithelial cells. A specific protein kinase A inhibitor, KT-5720, inhibited subsequent isoproterenol augmentation of THP-1 cell adhesion, further supporting the role of cAMP-dependent mechanisms in modulating THP-1 cell adhesion to HBECs.

Adrenergic beta-Agonists↗

PubMed2000

Sodium nitroprusside augments human lung fibroblast collagen gel contraction independently of NO-cGMP pathway.

Nitric oxide (NO) relaxes vascular smooth muscle in part through an accumulation of cGMP in the target cells. We hypothesized that a similar effect may also exist on collagen gel contraction mediated by human fetal lung (HFL1) fibroblasts, a model of wound contraction. To evaluate this, HFL1 cells were cultured in three-dimensional type I collagen gels and floated in serum-free DMEM with and without various NO donors. Gel size was measured with an image analyzer. Sodium nitroprusside (SNP, 100 microM) significantly augmented collagen gel contraction by HFL1 cells (78.5 +/- 0.8 vs. 58.3 +/- 2. 1, P < 0.01), whereas S-nitroso-N-acetylpenicillamine, 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride, NONOate, and N(G)-monomethyl-L-arginine did not affect the contraction. Sodium ferricyanide, sodium nitrate, or sodium nitrite was not active. The augmentory effect of SNP could not be blocked by 1H-[1,2, 4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, whereas it was partially reversed by 8-(4-chlorophenylthio) (CPT)-cGMP. To further explore the mechanisms by which SNP acted, fibronectin and PGE(2) production were measured by immunoassay after 2 days of gel contraction. SNP inhibited PGE(2) production and increased fibronectin production by HFL1 cells in a concentration-dependent manner. CPT-cGMP had opposite effects on fibronectin and PGE(2) production. Addition of exogenous PGE(2) blocked SNP-augmented contraction and fibronectin production by HFL1 cells. Therefore, SNP was able to augment human lung fibroblast-mediated collagen gel contraction, an effect that appears to be independent of NO production and not mediated through cGMP. Decreased PGE(2) production and augmented fibronectin production may have a role in this effect. These data suggest that human lung fibroblasts in three-dimensional type I collagen gels respond distinctly to SNP by mechanisms unrelated to the NO-cGMP pathway.

Animals↗

PubMed2000

Blood monocytes attenuate lung fibroblast contraction of three-dimensional collagen gels in coculture.

Mononuclear phagocytes can interact with mesenchymal cells and extracellular matrix components that are crucial for connective tissue rearrangement. We asked whether blood monocytes can alter matrix remodeling mediated by human lung fibroblasts cultured in a three-dimensional collagen gel. Blood monocytes from healthy donors (>95% pure) were cast into type I collagen gels that contained lung fibroblasts. Monocytes in coculture inhibited the fibroblast-mediated gel contractility in a time- and concentration-dependent manner. The concentration of PGE(2), a well-known inhibitor of gel contraction, was higher (P < 0.01) in media from coculture; this media attenuated fibroblast gel contraction, whereas conditioned media from either cell type cultured alone did not. Three-dimensional cultured monocytes responded to conditioned media from cocultures by producing interleukin-1beta and tumor necrosis factor-alpha, whereas fibroblasts increased synthesis of PGE(2). Antibodies to interleukin-1beta and tumor necrosis factor-alpha blocked the monocyte inhibitory effect and reduced the amount of PGE(2) produced. The ability of monocytes to block the fibroblast contraction of matrix may be an important mechanism in regulating tissue remodeling.

Cell Culture Techniques↗

PubMed1999

Th2-type cytokines modulate IL-6 release by human bronchial epithelial cells.

The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.

Bronchi↗

PubMed1999

IL-4 and IL-13 stimulate human bronchial epithelial cells to release IL-8.

Cytokine networks are important in regulating the traffic of inflammatory cells in the airways. Interleukin-8 (IL-8) released by human bronchial epithelial cells (HBECs) is thought to be of particular importance in attracting neutrophils and monocytes to sites of inflammation. Increased release of IL-8 by HBECs in response to Th-1 cytokines such as TNF alpha and IL-1 beta may be an important pathophysiologic pathway. The present study was designed to explore the role of the Th2 cytokine IL-4 and the functionally related interleukins IL-10, and IL-13 on the regulation of IL-8 release by HBECs. HBECs (passage 4-6) were cultured in LHC9/RPMI and when confluent cells were stimulated in unsupplemented medium LHCD/RPMI by IL-4, IL-10, and IL-13 at 10 ng/ml concentration for all cytokines. TNF alpha stimulation was used as a positive control. After 24 hours supernatants were collected and tested for IL-8 by a sandwich ELISA. Unstimulated HBECs spontaneously released limited amounts of IL-8 (11 +/-1 pM) and significantly increased cytokine production in response to IL-4 (42 +/- 1 pM), IL-13 (30 +/- 1 pM) and TNF (128 +/- 11 pM). Stimulation with IL-10 (11 +/- pM) did not change basal production of IL-8. When HBECs were co-stimulated with IL-4 plus TNF, the production of IL-8 was further increased (204 +/- 5 pM). In contrast, IL-10 attenuated the effect of TNF during co-stimulation (82 +/- 5 pM). IL-13 did not affect the release of IL-8 induced by TNF (111 +/- 9 pM). Northern blot analysis of IL-8 mRNA levels showed the highest induction of IL-8 mRNA in HBECs co-stimulated with TNF and IL-4. We conclude from our study that IL-4 directly induces IL-8 release from HBECs and amplifies the release of IL-8 in response to TNF alpha. IL-13 is less active and IL-10 has an inhibitory effect. Airway epithelial cells are able to interact, therefore, with products of both Th1 and Th2 cells with respect to modulating release of IL-8.

Bronchi↗

PubMed1999

IL-4 induces ICAM-1 expression in human bronchial epithelial cells and potentiates TNF-alpha.

Interleukin (IL)-4 is thought to contribute to the Th2 type of immune response and hence the development of allergic reactions such as asthma. In asthmatic patients, the airway epithelium expresses increased amounts of the cell surface adhesion molecule intercellular adhesion molecule (ICAM)-1 (CD54). One cytokine capable of inducing ICAM-1 in airway epithelial cells, tumor necrosis factor-alpha (TNF-alpha), is present in asthma. This study evaluated if IL-4 either alone or together with TNF-alpha costimulation might modulate CD54 expression by human bronchial epithelial cells (HBECs). CD54 positivity increased in response to IL-4 (16 +/- 2% positive vs. 3 +/- 1%, P < 0.01); greater induction of CD54 resulted from TNF-alpha (45 +/- 2%, P < 0.001). Costimulation with TNF-alpha plus IL-4 further augmented expression (56 +/- 1%, P < 0.05). Immunoperoxidase results were confirmed by flow cytometry. RT-PCR revealed no increase in ICAM-1 mRNA expression under control conditions or after stimulation with IL-4 alone. TNF-alpha increased IL-4 mRNA, and IL-4 potentiated this. Functionally, IL-4 augmented the adhesion of THP-1 monocyte/macrophage cells to monolayers of HBECs both alone and in the presence of TNF-alpha. We conclude that 1) IL-4 augments epithelial cell ICAM-1 expression, 2) IL-4 potentiates the adhesion of THP-1 monocyte/macrophage cells to epithelial cells, and 3) modulation of epithelial cell ICAM-1 expression by IL-4 may play a role in the immunopathology of bronchial asthma.

Bronchi↗

PubMed1999

Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels.

In the present study, we tested the hypothesis that neutrophil elastase (NE) might mediate remodeling of extracellular matrix by affecting fibroblast-mediated contraction of three-dimensional collagen gels. Human lung fibroblasts were cast into type I collagen gels containing NE. After gelation, the gels were released into medium and the area was measured by image analyzer. NE augmented gel contraction (p < 0.001). This was not due to cell proliferation or to degradation to soluble collagen fragments because the amounts of DNA and hydroxyproline were not altered. alpha1-Protease inhibitor and the synthetic inhibitor of NE, L-680,833, when added in sufficient amount to inhibit free elastase activity, blocked the contraction induced by NE. Furthermore, neutrophil granulocytes (PMN) in coculture, as well as conditioned media from PMN, resulted in an increased contractility (p < 0.001 for both). Bronchoalveolar lavage fluid (BALF) from patients with increased PMN in their lower respiratory tract and free elastase activity had augmentive activity for gel contraction which could be partially blocked by the inhibitors. We conclude that NE augments fibroblast-mediated contraction of collagen gels. The findings support the notion that products secreted by PMN in inflammatory disorders may lead to rearrangement of extracellular matrix and could subsequently lead to tissue dysfunction.

Adult↗

PubMed1999

Thoracic complications related to bone marrow transplantation.

Although progress has been made in the diagnosis and management of respiratory complications after BMT, such complications are still frequent and are a major cause of morbidity and mortality. The use of CMV-negative marrow and blood products, surveillance bronchoscopies, and prophylactic use of antivirals have significantly reduced the incidence of CMV pneumonia. DNA amplification techniques have allowed earlier detection of viral respiratory infections, and early detection of localized invasive aspergillosis can improve survival with lung resection and antifungal therapy. Finally, consideration for open lung biopsy should include the patient's degree of preoperative respiratory impairment, because this may relate to early postoperative survival.

Bone Marrow Transplantation↗

PubMed1998

Fibronectin production by cultured human lung fibroblasts in three-dimensional collagen gel culture.

In vivo, fibroblasts are distributed in a three-dimensional (3-D) connective tissue matrix. Fibronectin is a major product of fibroblasts in routine cell culture and is thought to regulate many aspects of fibroblast biology. In this context, we sought to determine if the interaction of fibroblasts with a 3-D matrix might affect fibronectin production. To examine this hypothesis, fibronectin production by fibroblasts cultured in a 3-D collagen gel or on plastic dishes was measured by ELISA. Fibroblasts in 3-D gel culture produced more fibronectin than those in monolayer culture. Fibroblasts in 3-D culture produced increasing amounts of fibronectin when the collagen concentration of the gel was increased. The 3-D nature of the matrix appeared to be crucial because plating the fibroblasts on the surface of a plastic dish underneath a collagen gel was not different from plating them on a plastic dish in the absence of collagen. In addition to increased fibronectin production, the distribution of the fibronectin produced in 3-D culture was different from that of monolayer culture. In monolayer culture, more than half of the fibronectin was released into the culture medium. In 3-D culture, however, approximately two-thirds remained in the collagen gel. In summary, the presence of a 3-D collagen matrix increases fibroblast fibronectin production and results in greater retention of fibronectin in the vicinity of the producing cells.

Blotting, Northern↗

PubMed1998

Human bronchial epithelial cells modulate collagen gel contraction by fibroblasts.

Connective tissue contraction is an important aspect of both normal wound healing and fibrosis. This process may contribute to small airway narrowing associated with certain airway diseases. Fibroblast-mediated contraction of a three-dimensional collagen gel has been considered a model of tissue contraction. In this study, the ability of primary cultured human bronchial epithelial cells (HBEC) obtained by bronchial brushings to modulate fibroblast gel contraction was evaluated. Human lung fibroblasts (HFL1) were cast into type I collagen gels. The gels were floated both in dishes containing a monolayer of HBEC or in dishes without HBEC. Contraction assessed by measuring the area of gels was increased at all time points from 24 h up to 96 h of coculture. At 48 h, coculture of HBEC with fibroblasts resulted in significantly more contraction than fibroblasts alone (36.6 +/- 1.2 vs. 20.4 +/- 1.7%, P < 0.05). Lipopolysaccharide (LPS, 10 micrograms/ml) stimulation of the HBEC augmented the contraction (44.9 +/- 1.0%, P < 0.05 vs. HBEC). In the presence of indomethacin, the augmentation by LPS was increased further (52.2 +/- 4.3%, P < 0.05 vs. HBEC with LPS), suggesting that prostaglandins (PGs) are present and may inhibit contraction. Consistent with this, PGE was present in HBEC-conditioned medium. Bronchial epithelial cell conditioned medium had an effect similar to coculturing. SG-150 column chromatography revealed augmentive activity between 20 and 30 kDa and inhibitory activity between 10 and 20 kDa. Measurement by enzyme-linked immunosorbent assay confirmed the presence of the active form of transforming growth factor (TGF)-beta 2. The stimulatory activity of conditioned medium was blocked by adding anti-TGF-beta antibody. These data demonstrate that, through the release of factors including TGF-beta 2 which can augment and PGE which can inhibit, HBEC can modulate fibroblast-mediated collagen gel contraction. In this manner, HBEC may modulate fibroblast activities that determine the architecture of bronchial tissue.

Animals↗

PubMed1998

Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction.

Cigarette smoking, the major cause of pulmonary emphysema, is characterized by destruction of alveolar walls. Because tissue destruction represents a balance between injury and repair, we hypothesized that cigarette smoke exposure may contribute to the development of emphysema through the inhibition of tissue contraction during the repair process. To partially evaluate this hypothesis, we investigated the effects of cigarette smoke extract (CSE) on the ability of cultured fibroblasts to mediate collagen gel contraction in vitro: CSE inhibited fibroblast-mediated gel contraction in a concentration-dependent manner (P < 0.01). Production of prostaglandin E2, a known inhibitor of fibroblast contraction, was unchanged by CSE as was cell surface integrin expression. In contrast, fibronectin production by fibroblasts was inhibited (P < 0.01), and addition of exogenous fibronectin partially restored the contractile activity, thus suggesting at least one mechanism to explain inhibition of gel contraction by CSE. When CSE was treated to remove volatile components, it showed less inhibitory activity on fibroblast-mediated gel contraction. Therefore, we also examined the effects of acrolein and acetaldehyde, two volatile components of cigarette smoke. Inhibition of contraction was observed at 5 microM acrolein and at 0.5 mM acetaldehyde. In conclusion, cigarette smoke inhibited fibroblast-mediated gel contraction, and this inhibition was due, at least in part, to the volatile components of cigarette smoke and may be mediated, at least in part, by a decrease in fibroblast fibronectin production. By inhibition of repair, these smoke components may contribute to the development of pulmonary emphysema.

Cell Survival↗

PubMed1997

Fibronectin.

Fibronectin is a glycoprotein consisting of repeating units of amino acids, which form domains that enable the molecule to interact with a variety of cells through both integrin and non-integrin receptors. It is encoded by a single gene, but alternative splicing of pre-mRNA allows formation of multiple isoforms that have critical roles in cell adhesion, migration and proliferation. The essential nature of fibronectin in development has clearly been demonstrated in a "knock-out" mouse model in which early lethality occurs. Fibronectin influences diverse processes including inflammation, wound repair, malignant metastasis, microorganism attachment and thrombosis. Researchers are currently developing tools, including synthetic peptides based on specific fibronectin regions. These molecules have been shown to alter processes such as lymphocyte binding in synovial tissue of rheumatoid arthritis, coronary arteriopathy in animal models of cardiac transplantation, and platelet aggregation in patients, and are thus providing important new therapeutic possibilities.

Alternative Splicing↗

PubMed1997

Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells.

Enhanced proliferation of airway smooth muscle is thought to contribute to the pathogenesis of asthma and other obstructive airway diseases. Lysophosphatidic acid (LPA) is a simple bioactive lipid mediator that stimulates mitogenesis in fibroblasts and some other cell types. The effects of LPA on mitogenesis of cultured human airway smooth muscle cells were determined by measuring [3H]thymidine incorporation into cellular DNA. LPA induced a concentration-dependent stimulation of [3H]thymidine incorporation of a similar magnitude to that induced by serum, with the effects of 50 microM LPA being similar to those of 5% serum. Stimulation by LPA and by serum was almost completely eliminated in cells exposed to pertussis toxin, indicating involvement of a pertussis toxin-sensitive G protein in mitogenic signaling by these agents. Epidermal growth factor (EGF) induced stimulation of a similar magnitude as that with LPA, but the stimulation by EGF was insensitive to pertussis toxin. LPA and EGF, when added together, exhibited a markedly synergistic stimulation of [3H]thymidine incorporation that was typically 10-fold greater than the stimulation with either agent alone. LPA and EGF also stimulated mitogenesis assessed by cell growth, and again LPA and EGF together exhibited synergism. These results suggest the possibility that stimulation of airway smooth muscle cell proliferation by LPA, either alone or by enhancing effects of other growth factors, could play a role in normal airway remodeling or in the pathological proliferation of smooth muscle in various airway diseases.

Cell Division↗

PubMed1997

Mutual inhibition by TGF-beta and IL-4 in cultured human bronchial epithelial cells.

The airway epithelial cell may play a role as an effector cell, releasing various cytokines and extracellular matrix components in immune responses, inflammation, and wound repair processes, thus contributing to cytokine "networks." The cytokines transforming growth factor (TGF)-beta and interleukin (IL)-4 are though to have pivotal roles in airway diseases, with IL-4 having proinflammatory actions and TGF-beta generally regarded to mediate repair and to attenuate immune responses. In asthma, where IL-4 and TGF-beta are thought to contribute to the inflammatory process and repair, respectively, interactions between these cytokines are likely to be of importance. Therefore, we studied the potential interaction of both cytokines by measuring IL-8 and fibronectin release by cultured human bronchial epithelial cells (HBECs). IL-4 is capable of inducing IL-8 release from HBECs. This effect of IL-4 can be blocked by the concurrent presence of the cytokine TGF-beta. In contrast, TGF-beta had a modest inconsistent stimulatory effect on IL-8 release by itself and had no effect on the IL-8 release induced by tumor necrosis factor (TNF)-alpha. An antagonistic effect of IL-4 and TGF-beta was also observed on HBEC fibronectin release. TGF-beta stimulated fibronectin release, and IL-4 was able to inhibit this. This effect was not due to a redistribution of fibronectin but appeared to be due to a true reduction in synthesis. Consistent with this, IL-4 and TGF-beta effects on IL-8 and fibronectin release were paralleled by changes in mRNA levels. The ability of TGF-beta to block IL-4-induced IL-8 release is certainly not the only mechanism to inhibit IL-8 release because dexamethasone was capable of inhibiting both TNF-alpha- and IL-4-induced release of IL-8. These results indicate that TGF-beta and IL-4 can have mutually inhibitory effects. The balance determined by this reciprocal inhibition may play an important role in regulating inflammation repair and in diseases such as asthma.

Adult↗

PubMed1997

Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells.

Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from cultured human bronchial epithelial cells was examined. CSE augmented IL-8 release from bronchial epithelial cells in a concentration- and time-dependent manner. Most of the augmenting activity of CSE on IL-8 release from bronchial epithelial cells was lost after volatilization or lyophilization treatment. Two major volatile factors in cigarette smoke, acrolein and acetaldehyde, augmented IL-8 release. Four cell strains were tested and showed increased IL-8 release in response to CSE. In addition, bronchoalveolar lavage was performed on 11 nonsmokers and 12 smokers. IL-8 concentration was greater in the proximal, bronchial samples than in distal, alveolar samples, and IL-8 in BAL from smokers was higher than in BAL from nonsmokers. There was a significant correlation between IL-8 concentration and neutrophil count in bronchial samples of BAL fluid. These data support the hypothesis that exposure to cigarette smoke may induce bronchial epithelial cells to release IL-8 and that this may contribute to airway inflammation in smokers.

Acetaldehyde↗