PMID- 35506423 OWN - NLM STAT- MEDLINE DCOM- 20220505 LR - 20220716 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 13 IP - 5 DP - 2022 May TI - Everolimus ameliorates Helicobacter pylori infection-induced inflammation in gastric epithelial cells. PG - 11361-11372 LID - 10.1080/21655979.2021.2018533 [doi] AB - Helicobacter pylori (H.pylori) infection caused by gastric mucosal inflammation plays a pivotal role in the progression of gastric diseases. The recruitment and attachment of monocytes to the gastric mucosal epithelium are a major event in the early stages of H. pylori-associated gastric diseases. Everolimus is a mechanistic/mammalian target of rapamycin (mTOR) inhibitor used to prevent tumor growth by inhibiting the PI3K signaling pathway. Here, we examined the pharmacological role of Everolimus against H.pylori-induced damage in gastric epithelial cells. Firstly, we found that Everolimus ameliorated H.pylori-induced oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Secondly, Everolimus significantly reduced the expressions of the pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-8. Moreover, it decreased the production of the pro-inflammatory chemokines C-X-C motif ligand 1 (CXCL1) and macrophage chemoattractant protein-1 (MCP-1). Importantly, Everolimus suppressed the induction of the adhesion molecule intracellular adhesion molecule-1 (ICAM-1) and the attachment of THP-1 monocytes to gastric epithelial AGS cells. Our data also shows that Everolimus inhibited the activation of the NF-kappaB signaling pathway. Therefore, we conclude that Everolimus could protect gastric epithelial cells by mitigating H.pylori-induced inflammatory response and the attachment of monocytes to epithelial cells. FAU - Liu, Jinglei AU - Liu J AD - Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to shandong First Medical University, Ji'nan City, Shandong Province, China. FAU - Zhang, Fangxu AU - Zhang F AD - Department of Gastrointestinal Surgery, Clinical College of Weifang Medical University, Weifang City, Shandong Province, China. FAU - Zhang, Zheming AU - Zhang Z AD - Department of Gastrointestinal Surgery, Clinical College of Weifang Medical University, Weifang City, Shandong Province, China. FAU - Zheng, Chunning AU - Zheng C AUID- ORCID: 0000-0002-9039-2065 AD - Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to shandong First Medical University, Ji'nan City, Shandong Province, China. LA - eng PT - Journal Article PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (Interleukin-8) RN - 9HW64Q8G6G (Everolimus) SB - IM MH - Epithelial Cells/metabolism MH - Everolimus/metabolism/pharmacology MH - *Helicobacter Infections/complications/drug therapy/metabolism MH - *Helicobacter pylori/metabolism MH - Humans MH - Inflammation/drug therapy/metabolism MH - Interleukin-8/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism PMC - PMC9276037 OTO - NOTNLM OT - Everolimus OT - Helicobacter pylori OT - NF-kappaB OT - gastritis OT - inflammation OT - monocyte attachment COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/05/05 06:00 MHDA- 2022/05/06 06:00 PMCR- 2022/05/04 CRDT- 2022/05/04 05:23 PHST- 2022/05/04 05:23 [entrez] PHST- 2022/05/05 06:00 [pubmed] PHST- 2022/05/06 06:00 [medline] PHST- 2022/05/04 00:00 [pmc-release] AID - 2018533 [pii] AID - 10.1080/21655979.2021.2018533 [doi] PST - ppublish SO - Bioengineered. 2022 May;13(5):11361-11372. doi: 10.1080/21655979.2021.2018533.