Pro-inflammatory cytokine IL-6 regulates LMO4 expression in psoriatic keratinocytes via AKT/STAT3 pathway.

Abstract

The transcription factor LIM-only protein 4 (LMO4) is overexpressed in the psoriatic epidermis and regulates keratinocyte proliferation and differentiation. High LMO4 expression levels are induced by interleukin-23 (IL-23) to activate the AKT/STAT3 signaling pathway. Interleukin-6 (IL-6) is mainly involved in regulating T cell functions and development in patients with psoriasis. However, whether LMO4 expression is regulated by IL-6 remains unclear. Therefore, the purpose of this study is to explore the role and molecular mechanisms of IL-6 in regulating LMO4 expression. The interleukin-6 (IL-6) levels in human plasma were determined using a chemiluminescence immunoassay system. A psoriasis-like mouse model was established using imiquimod induction. Epidermal keratinocytes (HaCaT) were cultured in defined keratinocyte-serum-free medium and stimulated by IL-6 alone or with inhibitors. The proteins of interest were detected using western blot analysis, immunofluorescence, and immunohistochemistry. The 5-ethynyl-2'-deoxyuridine assay was used to detect cell proliferation. The results revealed that IL-6 levels were markedly increased in the plasma of patients with psoriasis, compared to healthy control. The high expression of LMO4 was consistent with high levels of IL-6, p-AKT, and p-STAT3 in the lesions of both psoriasis patients and imiquimod-induced psoriasis-like mice. IL-6 activates the AKT/STAT3 signaling pathway, followed by LMO4 high-expression in HaCaT cells. IL-6 induces HaCaT proliferation and differentiation via AKT/STAT3 signaling pathway activation. We think that the high expression of LMO4 in psoriatic keratinocytes requires IL-6 to activate the AKT/STAT3 signaling pathway and leads to epidermal keratinocytes abnormal proliferation and differentiation.