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PubMed2000

MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration.

Exposure of eukaryotic cells to extracellular stimuli results in activation of mitogen-activated protein kinase (MAPK) cascades composed of MAPKs, MAPK kinases (MAP2Ks), and MAPK kinase kinases (MAP3Ks). Mammals possess a large number of MAP3Ks, many of which can activate the c-Jun N-terminal kinase (JNK) MAPK cascade when overexpressed, but whose biological function is poorly understood. We examined the function of the MAP3K MEK kinase 1 (MEKK1) in proinflammatory signaling. Using MEKK1-deficient embryonic stem cells prepared by gene targeting, we find that, in addition to its function in JNK activation by growth factors, MEKK1 is required for JNK activation by diverse proinflammatory stimuli, including tumor necrosis factor alpha, IL-1, double-stranded RNA, and lipopolysaccharide. MEKK1 is also essential for induction of embryonic stem cell migration by serum factors, but is not required for activation of other MAPKs or the IkappaB kinase signaling cascade.

Animals↗

PubMed2000

A generalized transport model for biased cell migration in an anisotropic environment.

A generalized transport model is derived for cell migration in an anisotropic environment and is applied to the specific cases of biased cell migration in a gradient of a stimulus (taxis; e.g., chemotaxis or haptotaxis) or along an axis of anisotropy (e.g., contact guidance). The model accounts for spatial or directional dependence of cell speed and cell turning behavior to predict a constitutive cell flux equation with drift velocity and diffusivity tensor (termed random motility tensor) that are explicit functions of the parameters of the underlying random walk model. This model provides the connection between cell locomotion and the resulting persistent random walk behavior to the observed cell migration on longer time scales, thus it provides a framework for interpreting cell migration data in terms of underlying motility mechanisms.

Anisotropy↗

PubMed1997

Matrix metalloproteinase-2 activation modulates glioma cell migration.

Stable transfection of U251.3 glioma cells with cDNA encoding MT-MMP-1 resulted in increased cell surface expression of MT-MMP-1 and TIMP-2, constitutive activation of MMP-2 proenzyme and increased collagen degradation. In tumor spheroid outgrowth assays, cell migration of MT-MMP-1 transfectants relative to control was enhanced on collagen and decreased on vitronectin and fibronectin. These effects were reversed by TIMP-2 and were not associated with any substantial changes in cell adhesion. Binding of U251.3 cells to the C-terminal domain of MMP-2 was specifically inhibited by anti-(alpha)vss3 integrin blocking antibody indicating that MMP-2 interacts with (alpha)vss3 through the enzyme's C-terminal portion at or near the integrin's matrix adhesion sites. We propose that these mechanisms could govern directed matrix degradation in the tumor cells' microenvironment by sequestration of active MMP-2 on the cell surface. Our data suggest that activation of MMP-2 and its proteolytic activity localized to the cell surface could differentially modulate tumor cell migration in response to particular matrix proteins by altering both composition of the extracellular matrix and expression of adhesion receptors on the cell surface.

Amino Acid Sequence↗

PubMed2001

Role of blood shear stress in the regulation of vascular smooth muscle cell migration.

Smooth muscle cell (SMC) migration from the media to the intima of blood vessels contributes to neointimal formation and atherogenesis. Here, we demonstrate how blood shear stress regulates vascular SMC migration in the encapsulating tissue of a micro-cylinder implanted in the center of the rat vena cava with the micro-cylinder perpendicular to blood flow. In this model, the micro-cylinder was exposed to a laminar flow with a known shear stress field in the leading region and a vortex flow in the trailing region. After surgery, the micro-cylinder was encapsulated by a thrombus-like tissue within one day, followed by SMC migration from the vena cava to the encapsulating tissue from day 3 to 20. SMC migration was time-dependent with a peak migration speed at day 5. At each given time (excluding day 1), blood shear stress exerts an inhibitory effect on SMC migration with significantly suppressed SMC migration in the laminar flow region than in the stagnation, separation, and vortex flow regions. SMCs were relatively parallel to the shear stress direction in high shear stress regions, whereas perpendicular to the shear stress direction in low shear stress regions. These results suggest that blood shear stress plays a role in regulating SMC migration and orientation in this model.

Animals↗

PubMed1996

Matrix-specific effect of endothelial control of smooth muscle cell migration.

PURPOSE: Smooth muscle cell (SMC) migration is a critical element in the development of intimal hyperplasia. The effect of endothelial cells (ECs) on SMC migration and the modulation of this cell-to-cell interaction by extracellular matrix is not well understood. METHODS: To examine this relationship SMCs and ECs were cocultured on opposite sides of a semipermeable membrane and were compared with SMCs cultured alone. To assess migration SMCs were plated at confluent density into the center of the membrane with a steel fence. After the fence was removed, SMCs were treated for 2 hours with mitomycin C (20 micrograms/ml) to assess migration independent of proliferation. Cell migration was measured with morphometry. Experiments were performed on plastic and membranes coated with fibronectin or type I collagen (n > or = 8/group). Cell adhesiveness was quantitated by cell attachment and spreading assays. RESULTS: ECs stimulated SMC migration by 187% when compared with SMCs cultured alone on plastic and by 160% when cultured on fibronectin (p < 0.01). Type I collagen stimulated migration of SMCs cultured alone and prevented EC stimulated migration in cocultured SMCs (p < 0.01). Cell adhesiveness was significantly increased in cocultured SMCs compared with SMCs cultured alone regardless of whether cells were cultured on plastic (EC/SMC, 13.5 +/- 0.6 SMCs/high power field vs SMC, 8.9 +/- 0.5, p < 0.01), fibronectin (16.3 +/- 0.8 vs 12.3 +/- 0.7, p < 0.01) or type I collagen (15.5 +/- 1.0 vs 12.4 +/- 0.6, p < 0.01). ECs increased SMC cell spreading on plastic and fibronectin when compared with SMCs cultured alone. No difference in SMC cell spreading was seen in the presence or absence of ECs when cells were cultured on type I collagen. EC-SMC contact was not required; EC-conditioned media alone increased SMC migration by 75% when compared with SMCs cultured alone. Our data suggest that ECs increase SMC migration by a diffusable molecule that may also alter SMC adhesion molecule expression. Extracellular matrix composition can attenuate these effects.

Animals↗

PubMed2002

Stripe provides cues synergizing with branchless to direct tracheal cell migration.

The Drosophila tracheal system is an interconnected tubular respiratory network, which is formed by directed stereotypic migration and fusion of branches. Cell migration and specification are determined by combinatorial signaling of several morphogens secreted from the ectoderm. We report the discovery of a group of ectodermal cells, marked by Stripe (Sr) expression, that coordinates tracheal cell migration in the dorsoventral axis. Sr, an EGR family transcription factor, is known to regulate muscle migration. In this study, we show that Sr ectodermal cells also provide signals that are utilized for tracheal migration. These cues are separated in the time course of embryonic development. Initially, tendon-precursor cells are in close proximity to the tracheal cells, and later, when tracheal migration is complete, the muscles displace the trachea and attach to the tendon cells. sr-mutant embryos exhibit defects in migration of all tracheal branches. Although the FGF ligand Branchless (Bnl) is expressed in a subset of tendon-precursor cells independently of Sr, Bnl functions cooperatively with proteins induced by Sr in attraction of tracheal branches.

Animals↗

PubMed2002

P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration.

p21-activated kinase 1 (PAK1) can affect cell migration (Price et al., 1998; del Pozo et al., 2000) and modulate myosin light chain kinase and LIM kinase, which are components of the cellular motility machinery (Edwards, D.C., L.C. Sanders, G.M. Bokoch, and G.N. Gill. 1999. Nature Cell Biol. 1:253-259; Sanders, L.C., F. Matsumura, G.M. Bokoch, and P. de Lanerolle. 1999. SCIENCE: 283:2083-2085). We here present a novel cell motility pathway by demonstrating that PAK4 directly interacts with an integrin intracellular domain and regulates carcinoma cell motility in an integrin-specific manner. Yeast two-hybrid screening identified PAK4 binding to the cytoplasmic domain of the integrin beta 5 subunit, an association that was also found in mammalian cells between endogenous PAK4 and integrin alpha v beta 5. Furthermore, we mapped the PAK4 binding to the membrane-proximal region of integrin beta 5, and identified an integrin-binding domain at aa 505-530 in the COOH terminus of PAK4. Importantly, engagement of integrin alpha v beta 5 by cell attachment to vitronectin led to a redistribution of PAK4 from the cytosol to dynamic lamellipodial structures where PAK4 colocalized with integrin alpha v beta 5. Functionally, PAK4 induced integrin alpha v beta 5-mediated, but not beta1-mediated, human breast carcinoma cell migration, while no changes in integrin cell surface expression levels were observed. In conclusion, our results demonstrate that PAK4 interacts with integrin alpha v beta 5 and selectively promotes integrin alpha v beta 5-mediated cell migration.

Amino Acid Sequence↗

PubMed1986

Experimental modification of postnatal cerebellar granule cell migration in vitro.

Histotypic migration of [3H]thymidine pulse-labeled granule cell neurons in cerebellar folium explants was monitored in the presence of antibodies to cell adhesion molecules and quantified by automatic image analysis. When explants were cultured in the presence of monovalent antibody fragments to cell adhesion molecules L1 and N-CAM, an inhibition of cell migration of 33.3 +/- 4.4% and 13.9 +/- 2.1%, respectively, was observed. In the presence of an equimolar mixture of monovalent antibody fragments to L1 antigen and N-CAM no additive effects in inhibition of cell migration were seen. Antibodies to the L2 carbohydrate epitope which is common to L1, N-CAM and other cell surface glycoproteins showed a similarly small effect on cell migration as antibodies to N-CAM. Monoclonal antibodies to cell surface antigen M2 and polyclonal antibodies to mouse liver membranes reacting with the surface of all cerebellar cell types did not alter the migratory behavior of granule cells. Cultivation of explants in the presence of neuraminidase, ganglioside binding toxins, as well as glycosaminoglycans and glycosaminoglycan degrading enzymes, also did not modify the extent of cell migration under the culture conditions used.

Animals↗

PubMed2006

Cell migration and polarity on microfabricated gradients of extracellular matrix proteins.

This paper explores the effects of the surface density and concentration profiles of extra cellular matrix proteins on the migration of rat intestinal IEC-6 cells. Microfluidic devices were used to create linear, immobilized gradients of laminin. This study investigated both the impact of the steepness and local concentrations on the directedness of cell migration. The bulk concentrations of proteins in the feed streams in the mixing device determined the gradient profile and the local concentration of laminin in the device. Two sets of gradients were used to explore cell migration directedness: (i) gradients with similar change in local concentration, i.e., the same gradient steepness, and (ii) different gradients with similar local concentrations. Cells migrated up the gradients, independent of the steepness of the gradients used in this study. At the same local laminin concentration, the migration rate was independent of the gradient steepness. However, cell directedness decreased significantly at high laminin densities.

Actins↗

PubMed2003

Inhibition of tendon cell migration by dexamethasone is correlated with reduced alpha-smooth muscle actin gene expression: a potential mechanism of delayed tendon healing.

Local corticosteroid injection is commonly used to treat sports-related tendon injuries. However, isolated cases of tendon rupture following injection suggest that this treatment may impair the healing process. Tendon healing requires the migration of tendon cells to the repair site, followed by the proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of dexamethasone on the migration of tendon cells intrinsic to rat Achilles tendon at concentrations similar to those typically used for local injection treatment. Furthermore, the existence of a correlation between this effect and the expression of the contractile actin isoform, alpha-smooth muscle (SM) actin, which is associated with cell motility, was also examined. Using cultured tendon cells, migration was evaluated by counting the number of initial outgrowths from the tendon explants and by transwell filter migration assay. The distribution and assembly of alpha-SM actin were assessed by immunocytochemistry. The mRNA and protein expressions of alpha-SM actin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Dose-dependent dexamethasone inhibition was demonstrated for both tendon cells outgrowth from the explants, ex vivo, and migration of tendon cells through the transwell filter, in vitro. Immunocytochemical staining revealed significant decreases in both the amount and assembly of alpha-SM actin in cells. Suppression of mRNA expression and protein level of alpha-SM actin was revealed from RT-PCR and Western blot analyses. In conclusion, dexamethasone inhibits tendon cell migration that is correlated with decreased gene expression of alpha-SM actin.

Achilles Tendon↗

PubMed1993

Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.

Recent findings indicate that variable expression of beta 1 integrins may play a role in differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their beta 1, alpha 2, alpha 3 and alpha 6 integrin subunit expression and cell migration on type IV collagen (CN IV) or laminin (LN). The MM cell line expressed markedly increased levels of the beta 1, alpha 2 and alpha 3, but not alpha 6 subunit compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly inhibited by function-blocking anti-beta 1 and anti-alpha 3 MAbs, but not by the anti-alpha 6 MAb tested. In contrast, the anti-alpha 2 MAb significantly inhibited MM but not PM cell migration. These data show that the alpha 3 subunit plays a significant role in melanoma cell motility on CN IV and LN and that the alpha 2 subunit has a significant contribution to the motility of the MM cell line.

Antibodies, Monoclonal↗

PubMed2003

TGF-beta1-mediated inhibition of HK-2 cell migration.

Restoration of proximal tubular cell (PTC) integrity and function after ischemic injury involves cell proliferation and migration. Hypoxia is a known stimulus for PTC TGF-beta1 synthesis. This study examines the effect of TGF-beta1 on PTC migration. A model of PTC injury was used consisting of mechanically wounding a monolayer of HK2 cells followed by repopulation of the denuded area by time lapse photomicroscopy. Repopulation was the result of cell migration but not proliferation. Addition of TGF-beta1 led to a marked inhibition of cell migration increased expression of paxillin and vincullin and their incorporation into dense focal adhesion plaques. This was associated with increased association of focal adhesion components with the f-actin cytoskeleton. There was also increased beta3 integrin expression and increased synthesis of the matrix component fibronectin. The effect on migration and focal adhesion reorganisation was abrogated by inhibitors of the RhoA downstream target ROCK, suggesting that signaling events resulting from altered beta3 integrin expression initiate the TGF-beta1 response. These results suggest that, by inhibition of cell migration, increased expression of TGF-beta1 after ischemia delays recovery of proximal tubule structure and function. We speculate that this may contribute to permanent alteration in renal tubular function after severe ischemic injury.

Cell Communication↗

PubMed2006

Epigenetic regulation of human trophoblastic cell migration and invasion.

Pivotal to successful mammalian reproduction is the ability of a developing embryo to implant to the uterine wall and establish a nutrient supply via placentation. Herein, we have examined the potential epigenetic regulation of human trophoblastic cell migration and invasion by use of the choriocarcinoma cell line, BeWo. Treatment of BeWo cells with a DNA methyltransferase inhibitor, 5'-aza-2'-deoxycytidine (AZA), resulted in conversion of cell morphology to a nonmigratory phenotype. This was exemplified by the ability of AZA to prevent BeWo cell migration in wound healing and transwell migration assays. AZA consequently inhibited BeWo cell invasion through reconstituted basement membrane. Examination of components of the adherens junction complex pivotal for determination of cell phenotype revealed that AZA specifically increased the mRNA level of E-cadherin and plakoglobin (gamma-catenin), but not alpha-catenin and beta-catenin. AZA also increased the gene promoter activity of both plakoglobin and E-cadherin. Protein levels of both plakoglobin and E-cadherin were increased by AZA, and AZA enhanced their localization to sites of intercellular contact. Forced expression of plakoglobin and E-cadherin abrogated BeWo cell migration, indicative that repression of these genes was required for BeWo cell migration. Small interfering RNA-mediated depletion of the individual DNA methyltransferase (DNMT) molecules did not affect plakoglobin and E-cadherin promoter activity or BeWo cell migration. However, increases in plakoglobin and E-cadherin promoter activity and inhibition of BeWo cell migration was achieved with small interfering RNA-mediated depletion of both DNMT-3a and DNMT-3b. Epigenetic regulation of plakoglobin and E-cadherin is therefore pivotal for appropriate trophoblastic invasion in vitro.

Azacitidine↗

PubMed1998

Antagonistic regulation of cell migration by epidermal growth factor and glucocorticoid in human gastric carcinoma cells.

Epidermal growth factor (EGF) induced the disruption and scattering of colonies of TMK-1, a cell line derived from a human gastric carcinoma. A stimulatory action of EGF on cell migration was also observed as determined by a wound assay. However, these actions of EGF were inhibited if the cells were pretreated with dexamethasone, a synthetic glucocorticoid. Dexamethasone increased cell adhesion to collagen type IV and laminin, but not to poly-L-lysine and fibronectin. In contrast, EGF did not affect cell adhesion to these extracellular matrices whether dexamethasone was present or not. Dexamethasone enhanced the protein levels of both alpha1 and beta1 integrin subunits, and that of the alpha1 beta1 heterodimer. Further, flow cytometric analysis revealed that dexamethasone increased the expression of beta1 and alpha1 integrin subunits at the cell surface, whereas EGF increased expression of beta1 and alpha2 subunits at the cell surface. Antibodies against alpha1 and beta1 integrin subunits inhibited the increased cell adhesion seen in the presence of dexamethasone. An immunofluorescence study indicated that dexamethasone increased the formation of focal adhesions along the entire edges of cell colonies. In contrast, EGF led to the formation of focal adhesions preferentially at the cell front, and this EGF-induced preferential formation was not observed if the cells were pretreated with dexamethasone. These results suggest that glucocorticoid increased cell adhesion to the extracellular matrix via alpha1 beta1 integrin, and thereby antagonized EGF-induced cell migration.

Cadherins↗

PubMed1983

A study of leukemic cell migration by an agarose plate method.

By means of inducing random migration of leukemic cells in human peripheral blood by an agarose plate method, a study was made to see how migration distance and cell morphology after migration differed with the type of leukemia. After 3 days of incubation, the distance of random migration in cells of lymphocytic leukemia patients was on the average 0.41 mm for the cells of 13 patients with adult T-cell leukemia/lymphoma and 0.03 mm for the cells of four patients with chronic lymphocytic leukemia which were all of B-cell origin. Thus leukemic cells of T-cell origin migrated farther than those of B-cell origin. In the cases of myelocytic leukemia, the distance of random migration was on the average 0.54 mm for the cells of five patients with acute myelocytic leukemia, 2.42 mm for the cells of three patients with acute myelomonocytic leukemia, 1.69 mm for the cells of four patients with chronic myelocytic leukemia at blastic crisis and 3.78 mm for the cells of one patient with chronic monocytic leukemia. Thus, cells of monocyte origin migrated quite well. Migrating cells differing from cells of smear samples retained their original natural morphology and were considered to serve as an aid in the differentiation of types of leukemia.

Adult↗

PubMed2002

A pivotal role for CC chemokine receptor 5 in T-cell migration to tumor sites induced by interleukin 12 treatment in tumor-bearing mice.

Interleukin (IL) 12 treatment in the CSA1M and OV-HM, but not in Meth A tumor models,induces tumor regression that is associated with T-cell migration to tumor sites.Here, we investigated the role of the CC chemokine receptor (CCR)5 in T-cell migration induced after IL-12 treatment. In the two IL-12-responsive tumor models (CSA1M and OV-HM), IL-12 treatment up-regulated the mRNA expression of CCR5 in splenic T cells as well as ligands for CCR5, such as macrophage inflammatory protein (MIP) 1alpha and MIP-1beta in tumor masses. In contrast, the expression of CCR5 in spleens and MIP-1alpha/MIP-1beta in tumor masses was marginally induced before and even after IL-12 treatment in the Meth A model in which T-cell migration is not observed. T cells infiltrating tumor masses in the former two IL-12-responsive models expressed CCR5. Administration of a synthetic CCR5 antagonist TAK-779 to tumor-bearing mice during IL-12 immunotherapy prevented T-cell migration and tumor regression. Furthermore, anti-CCR5 antibody was found to inhibit T-cell migration in the lymphoid cell migration assay. Namely, although splenic T cells prepared from IL-12-treated CSA1M or OV-HM-bearing mice migrated into the corresponding tumor masses in recipient mice, the migration was inhibited when donor T cells were treated with anti-CCR5 antibody before the injection. These results indicate a critical role for CCR5 in the induction of T-cell migration to tumor sites after IL-12 treatment.

Amides↗

PubMed2000

Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis.

E- and N-cadherin are calcium-dependent cell adhesion molecules that mediate cell-cell adhesion and also modulate cell migration and tumor invasiveness. The loss of E-cadherin-mediated adhesion has been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. However, recent evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. These findings have raised the possibility that N-cadherin contributes to the invasive phenotype. To determine whether N-cadherin promotes invasion and metastasis, we transfected a weakly metastatic and E-cadherin-expressing breast cancer cell line, MCF-7, with N-cadherin and analyzed the effects on cell migration, invasion, and metastasis. Transfected cells expressed both E- and N-cadherin and exhibited homotypic cell adhesion from both molecules. In vitro, N-cadherin-expressing cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered more efficiently to monolayers of endothelial cells. All cells produced low levels of the matrix metalloproteinase MMP-9, which was dramatically upregulated by treatment with FGF-2 only in N-cadherin-expressing cells. Migration and invasion of Matrigel were also greatly enhanced by this treatment. When injected into the mammary fat pad of nude mice, N-cadherin-expressing cells, but not control MCF-7 cells, metastasized widely to the liver, pancreas, salivary gland, omentum, lung, lymph nodes, and lumbar spinal muscle. The expression of both E- and N-cadherin was maintained both in the primary tumors and metastatic lesions. These results demonstrate that N-cadherin promotes motility, invasion, and metastasis even in the presence of the normally suppressive E-cadherin. The increase in MMP-9 production by N-cadherin-expressing cells in response to a growth factor may endow them with a greater ability to penetrate matrix protein barriers, while the increase in their adherence to endothelium may improve their ability to enter and exit the vasculature, two properties that may be responsible for metastasis of N-cadherin-expressing cells.

Animals↗

PubMed2004

Differential expression of cytokines in UV-B-exposed skin of patients with polymorphous light eruption: correlation with Langerhans cell migration and immunosuppression.

BACKGROUND: Disturbances in UV-induced Langerhans cell migration and T helper (T(H)) 2 cell responses could be early steps in the pathogenesis of PLE. OBJECTIVE: To establish whether UV-B exposure induces aberrant cytokine expression in the uninvolved skin of patients with polymorphous light eruption (PLE). DESIGN: Immunohistochemical staining and comparison of microscopic sections of skin irradiated with 6 times the minimal dose of UV-B causing erythema and the unirradiated skin of patients with PLE and of healthy individuals. SETTING: University Medical Center (Dutch National Center for Photodermatoses). Patients Patients with PLE (n = 6) with clinically proven pathological responses to UV-B exposure and normal erythemal sensitivity. Healthy volunteers (n = 5) were recruited among students and hospital staff. MAIN OUTCOME MEASURES: Expression of cytokines related to Langerhans cell migration (interleukin [IL] 1, IL-18,and tumor necrosis factor [TNF] alpha); T(H)2 responses (IL-4 and IL-10); and T(H)1 responses (IL-6, IL-12, and interferon gamma). Double staining was performed for elastase (neutrophils), tryptase (mast cells), and CD36 (macrophages). RESULTS: The number of cells expressing IL-1beta and TNF-alpha was reduced in the UV-B-exposed skin of patients with PLE compared with the skin of healthy individuals (P<.05 for TNF-alpha). No differences were observed in the expression of T(H)1-related cytokines but fewer cells expressing IL-4 infiltrated the epidermis of patients with PLE 24 hours after irradiation (P =.03). After UV exposure TNF-alpha, IL-4, and, to a lesser extent, IL-10 were predominantly expressed by neutrophils. CONCLUSIONS: The reduced expression of TNF-alpha, IL-4, and IL-10 in the UV-B-irradiated skin of patients with PLE appears largely attributable to a lack of neutrophils, and is indicative of reduced Langerhans cell migration and reduced T(H)2 skewing. An impairment of these mechanisms underlying UV-B-induced immunosuppression may be important in the pathogenesis of PLE.

Adult↗