interleukin-8 and Lichen-Planus

Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL-17-disorder, there is some evidence that Th1/IFN-ɣ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well-characterized inflammation present in PSO skin. First, we analysed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B and IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltrate mainly composed by CD3

Topics: Adolescent; Adult; Aged; CD4-Positive T-Lymphocytes; Child; Cytokines; Female; Gene Expression; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-17; Interleukin-8; Interleukins; Janus Kinase 1; Lichen Planus; Male; Middle Aged; Psoriasis; RNA, Messenger; STAT1 Transcription Factor; Young Adult

IL-33, a member of the IL-1 family, is implicated in type 2 T helper cell immune reactions and acts as an "alarmin" to induce activation of dendritic cells in response to external stimuli. We investigated the effect of inflammatory cytokines on IL-33 expression in normal human epidermal keratinocytes. IFN-γ dose- and time-dependently induced IL-33 expression in protein and mRNA; this was dependent on extracellular signal-regulated kinase, p38, EGFR, and JAK phosphorylation. Combined IFN-γ and tumor necrosis factor (TNF)-α treatment induced expression of a 20-kDa band corresponding to mature IL-33, which was abolished by the addition of a calpain inhibitor. The addition of the inhibitor to IFN-γ and TNF-α-stimulated cells also induced strong expression of a 25-kDa band. Small interference (si) RNA for IL-33 abolished expression of the smaller bands and the 30-kDa IL-33 band, suggesting that these IL-33 forms were IL-33 transcription products. Recombinant IL-33 added in the medium induced IL-8 production, and RNA knockdown by siRNA enhanced IL-8 expression, suggesting its dual role as a cytokine and a nuclear factor. These results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-γ and TNF-α are present in high levels.

Topics: Calpain; Cells, Cultured; Dermatitis, Atopic; Epidermal Cells; Epidermis; Foreskin; Gene Expression; Humans; Infant, Newborn; Interferon-gamma; Interleukin-33; Interleukin-8; Interleukins; Keratinocytes; Lichen Planus; Male; MAP Kinase Signaling System; Psoriasis; RNA Interference; Skin Diseases; Tumor Necrosis Factor-alpha

Folliculitis decalvans (FD) is a rare variant of primary cicatricial alopecia, for which the etiopathogenesis remains unclear. Our purpose was to evaluate whether certain immunologic mechanisms might have a significant role in the pathogenesis of FD. Lesional scalp biopsy specimens from 7 patients with FD, 7 with lichen planopilaris, and 4 with alopecia areata were studied immunohistochemically by using monoclonal antibodies to CD1a, CD3, CD4, CD8, CD20, CD25, HLA-DR, interleukin (IL)-1beta, IL-4, IL-8, interferon gamma, tumor necrosis factor alpha, basic fibroblast growth factor (b-FGF), transforming growth factor (TGF)-beta, endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule. We showed that early FD lesions are characterized by an infiltration of activated T-helper cells, featuring mixed TH1/TH2 polarization. IL-8 and ICAM-1 may contribute to the infiltration of neutrophils, whereas b-FGF and TGF-beta may represent important mediators of the fibrosis that characterizes late-phase FD.

Topics: Adult; Aged; Alopecia; Alopecia Areata; Female; Fibroblast Growth Factor 2; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Interleukin-8; Lichen Planus; Male; Middle Aged; T-Lymphocytes; Transforming Growth Factor beta