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Oncostatin M (OSM), a member of the gp130 cytokine family, is involved in T H 2 inflammation, epidermal integrity, and fibrosis. The effect of OSM on MCP-1 was evaluated with and without interleukin (IL)-4, IL-13, and anti-OSM receptor b (OSMRb) monoclonal antibody, KPL-716, in human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) in vitro. Cells were stimulated with OSM, leukemia inhibitory factor (LIF), IL-31, IL-13, alone or in combination, and separately with OSM, OSM+IL-4, and increasing concentrations of KPL-716. MCP-1 levels in supernatants were determined by ELISA. MCP-1 and receptor chain mRNAs were measured (Nanostring). OSM (50 ng/mL) strongly induced MCP-1 protein (P<.

Psoriasis skin is thought to be resistance for skin infection compared to atopic dermatitis because of the presence of abundant antimicrobial peptides in the epidermis. The key molecule which regulates the pathogenesis of psoriasis and determines the susceptibility to skin infection has not been known. Recently, IkBz (Nfkbiz) was identified as one of the susceptibility genes of psoriasis. To address the role of IkBz in the epidermis, we developed the mice lacking IkBz in the epidermis (Nfkbiz DK5 ). Although skin inflammation was weakened in Nfkbiz DK5 mice in the IL-23-induced psoriasis mode, skin inflammation was unexpectedly exacerbated in Nfkbiz DK5 mice in the IMQ-induced psoriasis model. Although skin colonization of gram-positive bacteria was recognized in both IMQ-treated mice, greater numbers of bacteria colonized in the follicles of the Nfkbiz DK5 mice. Oral antibiotics administration significantly reduced the skin inflammation in both mice, but there still remained the pathological features of psoriasiform dermatitis in control mice but not in Nfkbiz DK5 mice. To evaluate the role of IkBz to the skin infection, we applied S.aureus on the shaved dorsal skin after tape-stripping. The number of S. aureus was significantly increased in the skin from Nfkbiz DK5 mice compared to that from control mice. Furthermore, we stimulated cultured keratinocytes with TLR2 agonists and culture supernatants of S. aureus. The expression of some antimicrobial peptides increased in the epidermis from control mice but not in that from Nfkbiz DK5 mice. Taken together, these data suggested epidermal IkBz expression contributed to the pathogenesis of psoriasis and also to susceptibility to infection due to lower expression of antimicrobial peptides.