Livin upregulation in keratinocytes of psoriasis patients to promote adhesion molecule expression.

Abstract

Activation of keratinocytes (KCs) is the main pathological feature of psoriasis. KCs recruit neutrophils by releasing various antimicrobial peptides and chemokines, which is also related to the expression of KC adhesion molecules. However, the regulatory mechanism governing their expression is still unclear. Livin, an inhibitor of theapoptosis protein family member involved in proliferation and metastasis of tumor cells, is significantly increased in psoriatic lesions. The aim of this study was to investigate the role of Livin in regulating adhesion molecule expression in KCs and release of chemokines that promote the activation and adhesion of neutrophils. The expression of Livin in psoriasis patients, imiquimod mouse model, and the combination of IL-17 alpha, IL-22, IL-1 alpha, OSM, and TNF-α (Mix M5)-treated HaCaT cells were detected by immunofluorescence staining, RT-qPCR, and ELISA. Livin-overexpression and knockdown in HaCaT cells transfected with HIV-1-based lentiviral vectors were used to study the function of Livin using RNA-seq. Moreover, differences in the expression of HaCaT cell adhesion molecules after regulation of Livin expression and activation of neutrophils in the co-culture model were verified. Livin was upregulated in the KCs of psoriasis patients, imiquimod mouse model and Mix M5-treated HaCaT cells compared with the control groups. Livin in HaCaT cells might regulate the expression of adhesion molecules in KCs. Thus, Livin may be a key effector molecule that regulates the expression of adhesion molecules in KCs and promotes the activation and adhesion of neutrophils.