Epidermal Hyperplasia In Psoriasis Research Articles

The Unknown Role of Periostin in Psoriatic Epidermal Hyperplasia.

Psoriasis is an inflammatory skin disease that affects 1-2% of the general population. The pathomechanism is based on type 1 immunological reactions. Hyperplasia of the epidermis in psoriasis is a result of disrupted epidermal architecture due to increased synthesis and expression of extracellular matrix proteins. In our study, we analyzed the involvement of periostin (POSTN) in the pathogenesis of psoriasis, as one of the extracellular matrix proteins belonging to the fasciclin family. The study group consisted of 70 patients with psoriasis, while the control group comprised 30 healthy individuals. The serum concentrations of POSTN, Il-6, Il-17, Il-22, TNF-α and IFN-γ were measured in all participants. The severity of psoriasis was determined using the PASI (Psoriasis Area and Severity Index) score. The presence of POSTN in biopsy samples of 50 patients was assessed using the direct immunofluorescence method. The results were subjected to statistical analysis. The serum concentrations of POSTN, Il-6, Il-17, Il-22, TNF-α and IFN-γ in the study group are significantly higher than in the control group. Positive correlation has been demonstrated between the PASI score and the investigated cytokines, but not with POSTN. There was no statistically significant correlation between the POSTN level and the cytokines levels. POSTN deposits were localized in the epidermis in 66% of patients with psoriasis. The role of POSTN in the pathogenesis of psoriasis remains unclear. The mechanisms inducing the synthesis and expression of POSTN in psoriatic skin are not yet fully understood. Further research is needed to enhance our understanding of the mechanism underlying epidermal hyperplasia in psoriasis.

Eukaryotic Initiation Factor 4E (eIF4E) as a Target of Anti-Psoriatic Treatment

Eukaryotic translation initiation factor 4E (eIF4E) has been known to play a critical role in the regulation of gene expression and essential cellular processes such as proliferation, apoptosis and differentiation. We explored herein its role in the pathophysiology of psoriasis. The inhibition of eIF4E by siRNA or briciclib, an eIF4E small molecule inhibitor, downregulated the expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (e.g. eIF1A, eIF2α, eIF3A, eIF3B, eIF5 and eIF6). This inhibition also abolished psoriatic inflammation in both the imiquimod and TGFß mouse model, as well as in a human 3D-psoriasis tissue model. Downregulation of eIF4E and the other eIFs by application of briciclib (particularly when given topically) was linked to the normalization of cellular proliferation, restoration of the inflammatory milieu and epidermal hyperplasia of psoriasis, and normalization of levels of pro-inflammatory cytokines (e.g. TNFα, IL-1b, IL-17 and IL-22), and as well as keratinocyte differentiation markers (e.g. KRT16 and FLG). These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up avenues for the development of novel topical anti-psoriatic treatment strategies by targeting eIF4E.

IL-17–Mediated Downregulation of miR-101 Facilitates the Expression of EZH2 to Promote Epidermal Hyperplasia in Psoriasis

IL-17–Mediated Downregulation of miR-101 Facilitates the Expression of EZH2 to Promote Epidermal Hyperplasia in Psoriasis

366 Blockade of IL-17A pathway downregulates increased Glut1 expression in keratinocytes in psoriasis lesions and may reduce epidermal hyperplasia in psoriasis

Epidermal hyperplasia is a characteristic histological feature in psoriasis, a chronic inflammatory skin disease of IL-23/IL-17A axis. Metabolically, proliferating cells require glucose uptake through glucose transporters. Indeed, keratinocytes in psoriasis lesions exhibit increased expression of Glut1, one of the most widely expressed glucose transporters. In addition, Glut1-deficient mice show impaired epidermal hyperplasia in mouse psoriasis models, suggesting that glucose metabolism through Glut1 is essential for epidermal hyperplasia in psoriasis.

Sonodynamic therapy by phase-transition nanodroplets for reducing epidermal hyperplasia in psoriasis.

The cross-talk between hyperproliferative keratinocytes and activated immune cells is responsible for the progression of psoriasis. The strategy to alleviate psoriasis through inhibiting the abnormal proliferation of keratinocytes remains challenging due to limited therapeutic effects and low skin penetration of drugs. Herein we designed an ultrasound-triggered phase-transition nanodroplet that could produce cavitation to enhance skin penetration and effectively generate reactive oxygen species (ROS) to induce keratinocyte apoptosis for psoriasis treatment. After ultrasound stimulation, the perfluoro-n-pentane (PFP) liquid core of the nanodroplets vaporized, and the Haematoporphyrin monomethyl ether (HMME) encapsulated in the nanodroplets generated plenty of intracellular ROS which caused the apoptosis of HaCat cells through inducing mitochondrial dysfunction. In addition, the blank nanodroplets successfully inhibited the secretion of IL-6 and TNF-α from macrophages and dendritic cells in vitro due to the anti-inflammatory effect of POPG. For the skin penetration test, the phase-transition nanodroplets could effectively accumulate in the epidermis of the skin and generate intracellular ROS. The in-vivo anti-psoriasis experiment demonstrated that the phase-transition nanodroplets relieved the symptoms of psoriasis lesion and inhibited epidermal hyperplasia through induction of cell apoptosis under ultrasound irritation. Meanwhile, the inflammatory cytokines in the skin lesion almost decreased to the normal baseline level after SDT. Collectively, this study demonstrated a new strategy to inhibit keratinocyte hyperproliferation for psoriasis management based on sonodynamic responded nanodroplets.

Interleukin-17A Drives IL-19 and IL-24 Expression in Skin Stromal Cells Regulating Keratinocyte Proliferation.

IL-17A has been shown to be up-regulated in psoriasis lesions and is central to psoriasis pathogenesis. IL-19, along with other IL-20 subfamily cytokines such as IL-20 and IL-24, is induced by IL-17A and contributes especially to epidermal hyperplasia in psoriasis. However, the regulation, cellular sources of IL-19 and whether targeting of IL-17A by biologics influence IL-19 expression is not completely understood. To investigate the regulation of IL-19 by IL-17A in psoriasis, the imiquimod-induced psoriasis mouse (IMQ) model was used. Enhanced expression of IL-17A in the IMQ model was achieved by anti-IL-10 antibody treatment. Assessments of skin inflammation macroscopically, by histology and flow cytometry, all confirmed increased psoriatic symptoms. Interestingly, depletion of IL-10 markedly upregulated IL-23/IL-17 pathway related cytokines followed by a significant increase in IL-19 and IL-24. The up-regulation of IL-19 and IL-24, but not IL-17A, coincided with increased keratinocyte proliferation. To investigate the cellular source and effects of biologics on IL-19, human skin fibroblasts from healthy controls and psoriasis patients were cultured alone or co-cultured with activated memory CD4+ T cells. Besides IL-1β, IL-17A induced direct expression of IL-19 and IL-24 in skin fibroblasts and keratinocytes. Importantly, intrinsic higher expression of IL-19 in psoriatic skin fibroblasts was observed in comparison to healthy skin fibroblasts. Neutralization of IL-17A in the human skin fibroblast-T cell co-culture system significantly suppressed IL-19 and IL-24 expression. Together, our data show that IL-17A-induced IL-19 and IL-24 expression in skin stromal cells contribute to keratinocyte proliferation.

Pentacyclic triterpene compounds from loquat leaves reduce skin inflammation and epidermal hyperplasia in psoriasis via inhibiting the Th17 cells

Psoriasis is a refractory inflammatory skin disease affecting 2 %–3 % of the world population, characterized by the infiltration and hyper-proliferation of inflammatory cells and aberrant differentiation of keratinocytes. Targeting the IL-23/ Th17 axis has been well recognized as a promising therapeutic strategy, as the IL-23/ Th17 signal plays a vital role in the pathology of psoriasis. Three pentacyclic triterpene compounds isolated from loquat leaves have been reported with significant inhibitory effects on RORγt transcription activity and Th17 cell differentiation, and excellent performance in preventing lupus nephritis pathogenesis. However, the potential effects of these pentacyclic triterpene compounds on psoriasis remain unknown. In this study, we demonstrated the potent therapeutic effects of these pentacyclic triterpene compounds on psoriasis. These three pentacyclic triterpene compounds significantly alleviated skin inflammation as well as aberrant keratinocyte proliferation in an imiquimod-induced mouse psoriasis model. These compounds also inhibited the infiltration of immune cells and the level of pro-inflammatory cytokine in the dermis, as well as the cells number and changed the cytokine profiling expression of Th17 cells. These compounds could reduce the amount of CD4+ and CD8+ T cells in local lymph node, but not in spleen, which is different from hydrocortisone, the positive control treatment. These results suggest better performance of these compounds than steroids on treating psoriasis with less side effects on the integrated immune system. In summary, our findings uncover the potent therapeutic effects of pentacyclic triterpene compounds on psoriasis, providing potential candidate compounds for drug development.

064 Therapeutic effects of Smad7-based protein on imiquimod-induced psoriatic lesions

Smad7 structurally consists of N- and C- terminal domains linked with a PY motif. It shuttles between nuclear and cytoplasm to exert different biological functions. Smad7 was overexpressed in epidermis of clinical psoriatic lesions, which was thought to contribute to epidermal hyperplasia in psoriasis. To address if this is the case, we assessed the role of Smad7 and its functional domains in IMQ-induced psoriatic pathogenesis using genetic and pharmacological approaches. K5.Smad7 mice, which express Smad7 transgene(Tg) by a keratin-5 promoter, were resistant to IMQ-induced psoriatic lesions, suggesting an anti-inflammatory effect of Smad7 overexpression.

990 Targeting metabolism reprogramming of keratinocytes improves psoriasis-like skin inflammation

Keratinocyte-intrinsic metabolic reprogramming is the major fuel to epidermal hyperplasia in psoriasis, yet the underlying cause is poorly understood. We report that in psoriatic lesions, Protein Phosphatase 6 (PP6) is diminished in the epidermis, and its levels negatively correlate with the disease severity. Mice with genetic deficiency of Pp6 in keratinocytes spontaneously develop psoriasis-like skin phenotype resembling psoriasis clinically, histologically, in its gene expression profile and in its response to therapy. Mechanistically, Pp6-/- keratinocytes rely on inordinate ornithine cycle and enhanced oxidative phosphorylation (OXPHOS) to hyper-proliferate, mediated by increased Arginase-1 (Arg1) production resulting from the activation of CCAAT/enhancer-binding protein beta (C/EBPβ) and elevated levels of mitochondrial respiration chain components. Treating imiquimod-induced mouse model of psoriasis with an arginase inhibitor or (and) an OXPHOS inhibitor markedly improves the skin inflammation. Thus, our data reveal for the first time the molecular basis and the functional significance of keratinocyte metabolic adaptations in psoriasis, bringing forth novel therapeutic strategies targeting keratinocyte metabolism to treat psoriasis.

Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions

Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis. When we analyzed template-DNA strand segregation in trypsin-dissociated human psoriatic keratinocytes using BrdU pulse-chase labeling, we found that the percentage of asymmetric segregation of BrdU was significantly increased in the cell pairs of psoriatic epidermal cells compared with normal epidermal cells. Furthermore, we also examined the effects of both interleukin (IL)-17A and IL-22 cytokines on the differentiation status of cultured human keratinocytes. The results indicated that both cytokines had synergistic effects on passage-one epidermal cell sheets derived from skin explants and also on cultured keratinocytes, were involved in the maintenance of the undifferentiated stem cell phenotype, and these results suggest an efficient mechanism for preventing the premature loss of basal stem-cell pools in the pro-inflammatory cytokine-enriched milieu of the psoriatic epidermis. Our findings suggest that inhibition of hyperactive stem cells represents a potential therapeutic target to combat recalcitrant epidermal hyperplasia in psoriasis.

Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis.

Psoriasis is a chronic recurrent inflammatory skin disorder characterized by the dysregulated cross-talk between epidermal keratinocytes and immune cells, leading to keratinocyte hyperproliferation. Several studies demonstrated that Wnt pathway genes were differentially expressed in psoriatic plaques and likely were involved in the pathophysiology of disease. However, the molecular mechanisms underlying Wnt signaling regulation in epidermal hyperplasia in psoriasis remain largely unknown. We report that the expression of secreted frizzled-related protein (SFRP) 4, a negative regulator of the Wnt signaling pathway, was diminished in lesional skin of mouse models and patients with psoriasis. SFRP4 directly inhibited excessive keratinocyte proliferation evoked by proinflammatory cytokines in vitro. Pharmacological inhibition of Wnt signaling or intradermal injection of SFRP4 decreased the severity of the psoriasiform skin phenotype in vivo, including decreased acanthosis and reduced leukocyte infiltration. Mechanistically, we identified that aberrant promoter methylation resulted in epigenetic downregulation of SFRP4 in inflamed skin of patients with psoriasis and in the IL-23-induced mouse model. Our findings suggest that this epigenetic event is critically involved in the pathogenesis of psoriasis, and the downregulation of SFRP4 by CpG island methylation is one possible mechanism contributing to the hyperplasia of epidermis in the disease.

Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

BackgroundEpidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. MethodsTo examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin's role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). ResultsPeriostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, −22, or −23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. ConclusionsPeriostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis.

Interleukin-17 Targets Ppp6c for epidermal hyperplasia via NF-kappaB-dependent MicroRNA miR-31 induction (HUM7P.300)

Abstract The efficacy of monoclonal antibodies against either interleukin (IL)-17 or the IL-17 receptor in psoriasis therapy provides strong evidence that IL-17 is the major inflammatory mediator in this disease. However, it is unclear how IL-17 induces epidermal basal keratinocyte hyperproliferation in psoriasis. To explore the mechanism of IL-17 in epidermal hyperplasia in psoriasis, we focused on microRNA(s) induced by IL-17 as these small non-coding RNAs play an important role in regulation of cellular proliferation. Among all the microRNAs we screened, microRNA-31 (miR-31) is the only one extremely sensitive towards IL-17 for its induction in keratinocytes. Its expression in both the epidermis of lesional skin of human psoriasis patients and mouse psoriasis models is IL-17 inducible and NF-kappaB dependent. A causal relationship between IL-17-dependent miR-31 induction and basal keratinocyte hyperproliferation has been then established by constructing and analyzing epidermal conditional knockout of miR-31 (miR-31fl/fl/Keratin 5-Cre) engineering animals. A careful genomic analysis led us to realize that miR-31 targets protein phosphatase 6 (ppp6c), a negative regulator restricting G1 to S phase progression. As expected, ppp6c is suppressed by IL-17 through the miR-31 induction and is diminished in human psoriatic epidermis. We thus have uncovered a novel mechanism that helps explain how T helper (Th)-17 cells signal to basal keratinocytes for their hyperproliferation in psoriasis.

Assessment of Leptin Gene Polymorphism rs2060713 in Psoriasis Vulgaris

Psoriasis is a lifelong disorder characterized by approximately 8-fold reduction of the duration of normal skin keratinocyte cell cycle and 2-fold increase of the number of dividing cells. Multiple genes, several environmental factors, and immune system alterations are involved in the pathogenesis of psoriasis. Hyperleptinemia is associated with psoriasis and leptin acts as an angiogenic factor. Angiogenetic processes precede the epidermal hyperplasia in psoriasis, indicating possible involvement of leptin in the pathogenesis of psoriasis. Leptin gene polymorphisms and their association with psoriasis have been given very little attention. We present a study of the rs2060713C/T genetic polymorphism in the pathogenesis of psoriasis vulgaris in 263 vulgaris patients and 252 unrelated matched healthy controls. No statistically significant differences were observed between patients and controls. A statistically nonsignificant trend was observed in males with the early onset type of psoriasis (11.1% C/T in patients versus 5.6% in controls) and in females with the late onset type of the disease (12.8% C/T in patients versus 3.3% in controls). Still, there is no hard evidence on correlation of psoriasis vulgaris with this polymorphism. Possible association with specific forms of the disease and either gender needs further investigation in larger studies.

The expression pattern of antiapoptotic protein c-FLIP in psoriatic epidermis

Background Psoriasis is a chronic, relapsing, inflammatory, and hyperproliferative disease. The pathological changes affecting skin in psoriasis are mainly driven by abnormal differentiation secondary to activation of T cells. Keratinocytes may undergo apoptosis by loss of cell-cell contact after crosslinking of the FAS (CD95) molecule. The epidermal hyperplasia in psoriasis has been implicated to be a result of suppression of apoptosis. A key inhibitor of death receptor signaling is cellular FLICE inhibitory protein (c-FLIP), which interacts with FAS-associated death domain protein (FADD) and procaspase-8 preventing it from binding to caspase-8, thereby inhibiting the initiation of the apoptotic cascade. Aim of work This study was designed to investigate the expression pattern of antiapoptotic molecule c-FLIP in psoriasis vulgaris patients. Materials and methods Twenty psoriasis vulgaris patients were enrolled in this study. All patients were subjected to assessment of the degree of severity using PASI score. A 2-mm punch biopsy was taken from each patient from lesional and nonlesional areas for evaluation of c-FLIP mRNA gene expression using RT-PCR. Results We found that there was a direct significant relationship between psoriasis and c-FLIP protein levels measured. The study also showed that the discrimination of the degree of severity of psoriasis using psoriatic skin c-FLIP mRNA level can be reliable, with 100% sensitivity, 81.2% specificity, and 85% accuracy. Conclusion Increased levels of c-FLIP might induce upregulation of keratinocyte proliferation and downregulation of the apoptotic signaling pathway in psoriatic epidermis. c-FLIP might be a potential new target for preventing keratinocyte proliferation in psoriasis in the future.

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis

T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.

The “Caveolae Brake Hypothesis” and the Epidermal Barrier

Epidermal permeability barrier formation depends upon lamellar body (LB) secretion/fusion with the apical plasma membrane (APM) of outermost stratum granulosum (SG) cell, creating cholesterol/glycosphingolipid-enriched lipid rafts-like domains. We found that the dimensions of these domains are comparable to lipid raft in other cell types; and that acute barrier disruption regulates their size and dynamics. To assess the function of these LB-derived raft-like domains, we assessed APM dynamics and barrier recovery in methyl-beta-cyclodextrin (MbetaCD)-treated hairless mice and caveolin-1 knockouts (cav-1(-/-)). MbetaCD treatment impaired APM raft-like domain formation and barrier recovery. Accelerated barrier recovery is observed in cav-1(-/-) in parallel with expansion of raft-like domains. Barrier abrogation of normal epidermis resulted in translocation of cav-1 from the cytoplasm to raft-like membrane domains, restricting further raft-like domain formation and initiating terminal differentiation. Inhibition of LB secretion by monensin and absence of cav-1 delayed terminal differentiation. Furthermore, cav-1(-/-) mice exhibited an increased propensity to develop experimentally induced epidermal hyperplasia correlating with lipid raft persistence. Finally, the epidermal hyperplasia in psoriasis and Netherton syndrome is paralleled by increased lipid raft formation. These studies demonstrate that cav-1 delivery to the APM by LB trafficking to APM "brakes" further LB secretion, signals terminal differentiation, and regulates epidermal hyperproliferation.

Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in human keratinocytes

The 12/15-lipoxygenase (12/15-LOX) pathways of arachidonate metabolism have been implicated in the pathogenesis of psoriasis. Since UV photo-therapy is a commonly used technique for inhibiting cell proliferation and inflammation in skin diseases, we hypothesized that UV-irradiation may affect 12/15-LOX expression which might regulate cell proliferation. In this study, we showed that UV-irradiation suppressed 12-LOX expression, whereas up-regulated 15-LOX expression. Treatment with the 15-LOX metabolites sufficiently suppressed insulin-like growth factor II-induced 12-LOX expression and blocked cell cycle progression. On the basis of our findings, we think that the 15-LOX metabolites may inhibit epidermal hyperplasia in psoriasis by regulating 12-LOX expression.

The role of heparin-binding EGF-like growth factor and amphiregulin in the epidermal proliferation of psoriasis in cooperation with TNFα

Heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AREG) are the members of EGF family that bind to common EGF receptor (EGFR) in the epidermis. However, the role of these two growth factors in epidermal hyperplasia of psoriasis has not been established. On the other hand, CD4+ T cells are responsible for the development of the psoriatic plaques. However, inflammatory cytokines, such as TNFalpha, IL-1beta and IFNgamma, inhibit the growth of human keratinocytes in vitro. The expression of HB-EGF, AREG and EGFR proteins in normal (n = 22) and psoriatic (n = 34) skin tissues was examined by immunohistochemistry. Then, the effects of HB-EGF and AREG on the growth of cultured adult normal human epidermal keratinocytes (NHEK-AD) with or without TH1 cytokines, such as TNFalpha, IL-1beta and IFNgamma, were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and the effects of these cytokines on the expression of EGFR mRNA in NHEK-AD were examined by real-time reverse transcriptase-polymerase chain reaction. The expression of HB-EGF and AREG in the epidermis was not specific to psoriatic plaques, but the distribution of positive cells throughout the epidermis was different between normal skins and psoriatic plaques. On the other hand, in the dermis and the papillary dermis, most of vascular endothelial cells and infiltrating mononuclear cells expressed both HB-EGF and AREG in normal skins and psoriatic plaques, and these positive cells were more frequent in psoriasis compared to normal skin. In the in vitro growth assay, HB-EGF, not AREG, stimulated the proliferation of NHEK-AD at the optimal concentration of 1 ng/ml. Furthermore, HB-EGF compensated the growth-suppressing effects of TNFalpha, IL-1beta and IFNgamma on NHEK-AD, and TNFalpha promoted the growth of NHEK-AD at the concentration of 2 and 20 U/ml in combination with HB-EGF and, in lesser extent, with AREG. However, TNFalpha did not affect the expression of EGFR mRNA in NHEK-AD. Growth factors and inflammatory cytokines produced in the dermis would be important for the epidermal proliferation in psoriatic plaques and TNFalpha may play a key role in cooperation with HB-EGF and AREG in the proliferation of epidermal keratinocytes at the psoriatic skin lesions.

In situ expression of interleukin-6 in psoriatic epidermis during treatment.

Interleukin-6 (IL-6) is a multipotential cytokine which may act as a growth factor for keratinocytes. The epidermal hyperplasia of psoriasis may be explained in part by an overproduction of this cytokine. We have previously shown by in situ hybridization that IL-6 mRNA is most strongly expressed in the peripheral lesion of an advancing psoriatic plaque. In the present study, we investigated whether there were differences between the expression of IL-6 in untreated psoriatic epidermis and the lesion during the course of clinical improvement. In the untreated psoriatic lesion, the weak expression of IL-6 mRNA was localized in the lower epidermis. However, IL-6 mRNA was not detected in the clearly improved lesion. In the improving lesion, with clinically less scaling, less induration, and histologically thinner epidermis, IL-6 mRNA-expressing keratinocytes were detectable in a greater proportion of the total epidermal components than in the untreated, fully developed lesion. These results showed that IL-6 mRNA was strongly expressed in lesions with moderate epidermal hyperproliferation, indicating that this cytokine may play a role in the transitional phase during the course of improvement as well as in the lesion's formation.