PMID- 36603482 OWN - NLM STAT- MEDLINE DCOM- 20230203 LR - 20230321 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 162 DP - 2023 Feb TI - Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages. PG - 156114 LID - S1043-4666(22)00323-4 [pii] LID - 10.1016/j.cyto.2022.156114 [doi] AB - Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Xia, Ting-Ting AU - Xia TT AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Hu, Rong AU - Hu R AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Shao, Cheng-Jie AU - Shao CJ AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Feng, Yan AU - Feng Y AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Yang, Xing-Le AU - Yang XL AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Xie, Yong-Peng AU - Xie YP AD - Emergency Department, the Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. FAU - Shi, Jia-Xin AU - Shi JX AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. Electronic address: shijiaxin919@126.com. FAU - Li, Jia-Shu AU - Li JS AD - Department of Pulmonary and Critical Care Medicine, The Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. Electronic address: ljssm1118@sina.com. FAU - Li, Xiao-Min AU - Li XM AD - Emergency Department, the Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of Kangda College of Nanjing Medical University, Affiliated Hospital of Jinzhou Medical University, 6 East Zhenhua Road, Lianyungang 222006, China. Electronic address: lyglxm1@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230103 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Immunologic Factors) RN - 130068-27-8 (Interleukin-10) RN - 0 (Lipopolysaccharides) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 76687-96-2 (teleocalcin) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Humans MH - Immunologic Factors/metabolism MH - Interleukin-10/metabolism MH - Lipopolysaccharides/pharmacology/metabolism MH - Macrophages, Alveolar/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - *Respiratory Distress Syndrome/metabolism MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - AKT OT - Human umbilical mesenchymal stem cells (HUMSC) OT - Interleukin-10 (IL-10) OT - Stanniocalcin-1 (STC-1) OT - mTOR COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/01/06 06:00 MHDA- 2023/01/17 06:00 CRDT- 2023/01/05 18:19 PHST- 2022/08/24 00:00 [received] PHST- 2022/11/24 00:00 [revised] PHST- 2022/12/19 00:00 [accepted] PHST- 2023/01/06 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] PHST- 2023/01/05 18:19 [entrez] AID - S1043-4666(22)00323-4 [pii] AID - 10.1016/j.cyto.2022.156114 [doi] PST - ppublish SO - Cytokine. 2023 Feb;162:156114. doi: 10.1016/j.cyto.2022.156114. Epub 2023 Jan 3.