A SFPQ/S100A8 Complex Is Formed by Activation of mTOR-p70S6K Pathway in Psoriasis

Objectives: Psoriasis is a chronic skin disease that causes a rash with itchy and scaly patches.Splicing factor proline-and glutamine-rich (SFPQ) and S100 calcium-binding protein A8 (S100A8) are multifunctional proteins involved in a variety of cellular processes.They are related to neurodegenerative and allergic diseases.This study aimed to investigate the mechanism involved in the formation of a SFPQ/S100A8 complex.Methods: Human keratinocytic HaCaT cells were treated with imiquimod (IMQ) to induce a psoriatic like inflammation.Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA).Protein expression and phosphorylation levels in control and IMQ-treated groups were analyzed by western blot.Immunocytochemistry was performed to examine colocalization of SFPQ and S100A8.Results: IMQ treatment markedly increased the expression of S100A8 and the translocation of SFPQ in the cytoplasm of HaCaT cells.It also increased the number of SFPQ/S100A8 complexes in the cytoplasm and the expression of tumor necrosis factor-, interferon-, interleukin (IL)-17A, and IL-22 in supernatants of HaCaT cells.Pretreatment with rapamycin (RAPA) suppressed the formation of the SFPQ/S100A8 complex by inhibiting the mTOR signaling pathway.It also reduced cytokine expression and promoted the recovery of filaggrin expression. Conclusion:Findings of this study suggest that the SFPQ/S100A8 complex is formed through activation of the mTOR-p70S6K pathway.The complex and mTOR might be a pathogenic factor and a potential drug candidate for psoriasis, respectively.