Abstract: Objective: To evaluate the effect of IL-17A on insulin resistance in keratinocytes and the relationship of keratinocyte insulin resistance with the severity of psoriasis. Methods: HaCaT cells were treated with 50 ng/mL IL-17A, and then Western blot analysis was performed to detect the expression level of downstream proteins of insulin receptors signaling pathways. The expression level of GLUT4 was detected by Western blot and cellular immunofluorescence. The PASI score was assessed and homeostasis model insulin resistance index (HOMA-IR) was calculated in 22 psoriasis patients in our hospital from January to Decemner 2019. The expression of p-IRS-1 (Ser636) in the lesions of patients was detected by immunohistochemistry. And then the correlations between the histochemistry score(H-score) and PASI, HOMA-IR were analyzed. Results: Compared with insulin group, the expression of p-IRS-1 (Ser636)/IRS-1 increased in the insulin+IL-17A group, and the expression of p-PKB (Ser437)/PKB and GLUT4 in HaCaT cells decreased (Ps<0.05). There was a positive correlation between H-score and PASI (r=0.456, P=0.033), and H-score was also positively correlated with HOMA-IR (r=0.613, P=0.004). Conclusion: IL-17A may induce the insulin resistance in HaCaT cells by suppressing the IRS-1/PI3K/PKB/GLUT4 signaling pathway, which may have a certain impact on the severity of psoriasis.

Key words: psoriasis, Interleukin-17A, keratinocyte, insulin resistance