Autophagy Inhibits Inflammation via Down-Regulation of p38 MAPK/mTOR Signaling Cascade in Endothelial Cells
Open Access
- 1 March 2023
- journal article
- research article
- Published by Taylor & Francis Ltd in Clinical, Cosmetic and Investigational Dermatology
- Vol. ume 16, 659-669
- https://doi.org/10.2147/ccid.s405068
Abstract
Objective: Autophagy, an intracellular process of self-digestion, has been shown to modulate inflammatory responses. In the present study, we determined the effects of autophagy on inflammatory response induced by M5 cytokines. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with M5 cytokines to induce inflammation. Expression levels of mRNA for inflammatory cytokines and BIRC2 were compared in HUVECs with vs without induction of autophagy with rapamycin (RAPA) by PCR, while cell apoptosis was assessed by flow cytometry and caspase-3 activity assay kit. Expression levels of LC3, p62, p-p38 MAPK (Thr180/Tyr182), p-mTOR (Ser2445) and p-ULK1 (Ser555) proteins were measured by Western blotting. The nitric oxide (NO) content, NO synthase (NOS) activity and cell angiogenesis were also evaluated. Results: Induction of autophagy with RAPA decreased expression levels of IL6, IL8 and CCL20, in addition to reduction in inflammation-induced apoptosis in HUVECs. Moreover, RAPA increased LC3II, while decreasing p62 expression. Likewise, expression levels of p-p38 MAPK and p-mTOR proteins were markedly decreased by the treatment with RAPA. Finally, RAPA treatment increased the NO content and the NOS activity, and inhibited angiogenesis. Conclusion: Induced autophagy can improve the function of endothelial cells in psoriasis, suggesting approaches to induce autophagy can be used to ameliorate psoriasis.Keywords
This publication has 47 references indexed in Scilit:
- Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal AgingScience, 2011
- Autophagy Controls IL-1β Secretion by Targeting Pro-IL-1β for DegradationOnline Journal of Public Health Informatics, 2011
- Autophagy in immunity and inflammationNature, 2011
- Eaten alive: a history of macroautophagyNature, 2010
- Mammalian autophagy: core molecular machinery and signaling regulationCurrent Opinion in Cell Biology, 2010
- New insights into the function of Atg9FEBS Letters, 2010
- ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for AutophagyOnline Journal of Public Health Informatics, 2009
- Novel targets for Huntington's disease in an mTOR-independent autophagy pathwayNature Chemical Biology, 2008
- Autophagy in the Pathogenesis of DiseaseCell, 2008
- Chapter 16 Methods for Distinguishing Apoptotic from Necrotic Cells and Measuring Their ClearanceMethods in Enzymology, 2008