IL‐17A is involved in the hyperplasia of blood vessels in local lesions of psoriasis by inhibiting autophagy

• Published in: Journal of cosmetic dermatology Vol. 23; no. 1; pp. 326 - 338
• Main Authors: Wang, Juanjuan, Zhou, Ling, Hou, Hui, Li, Jiao, Zhao, Xincheng, Li, Jiajie, Li, Junqin, Niu, Xuping, Hou, Ruixia, Zhang, Kaiming
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2024
• Subjects: AMP-Activated Protein Kinases - pharmacology; AMP-Activated Protein Kinases - therapeutic use; AMPK; Angiogenesis; Antibodies; Apoptosis; Autophagy; Blood vessels; Cell culture; Endothelial Cells - pathology; Experiments; Flow cytometry; Humans; Hyperplasia; IL‐17A; Inflammation; Inflammation - pathology; Interleukin-17 - metabolism; Pathogenesis; Pathogens; Protein expression; Proteins; Psoriasis; Psoriasis - drug therapy; Software; Statistical analysis; Variance analysis; Vascular endothelial growth factor; AMPK; autophagy; IL-17A; inflammation; angiogenesis
• ISSN: 1473-2130; 1473-2165
• DOI: 10.1111/jocd.15975

Objective Increased angiogenesis is a pathological feature of psoriasis, but the pathomechanisms of angiogenesis in psoriasis are not clear. Interleukin‐17A (IL‐17A) is the major effect factor in the pathogenesis of psoriasis. Our results showed that IL‐17A can promote angiogenesis and cause endothelial cell inflammation. Autophagy plays an important role not only in regulating inflammation, but also in regulating angiogenesis. Whether angiogenesis in psoriasis is related to autophagy remains unclear. In this study, we treated human umbilical vein endothelial cells (HUVECs) with IL‐17A to simulate increased angiogenesis to study whether increased angiogenesis in psoriasis is related to autophagy. Methods and Results Our results showed that treatment of HUVECs with IL‐17A significantly increased angiogenesis and expression levels of mRNA for multiple proinflammatory cytokines (CCL20, IL‐8, CCL2, IL‐6, and IL‐1β) and, while decreasing intracellular levels of nitric oxide (NO) and NO synthase (NOS) activity. Moreover, IL‐17A inhibited autophagy as shown that IL‐17A significantly increased expression levels of LC3II and p62 proteins. Induction of autophagy ameliorated IL‐17A‐mediated inflammatory response and inhibited angiogenesis, accompanied by increased p‐AMPKα(Thr172) and p‐ULK1(Ser555) expression, and decreased p‐mTOR(Ser2448) and p‐ULK1(Ser757) expression. Furthermore, inhibition of either AMPK or lysosomal acidification completely overrode autophagy‐induced changes in angiogenesis and NOS activity. Finally, induction of autophagy decreased apoptosis and caspase‐3 activity in IL‐17A‐treated HUVECs. Conclusions These results showed that IL‐17A is involved in angiogenesis and inflammatory response by inhibiting autophagy through AMPK signaling pathway, suggesting that autophagy may be a new therapeutic target for psoriasis.