PMID- 34426780 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20240226 IS - 2210-7185 (Electronic) IS - 2210-7177 (Print) IS - 2210-7177 (Linking) VI - 2021 DP - 2021 TI - hucMSC Conditioned Medium Ameliorate Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Oxidative Stress and Inflammation via Nrf2/NF-kappaB Signaling Pathway. PG - 6653681 LID - 10.1155/2021/6653681 [doi] LID - 6653681 AB - Acute lung injury (ALI) is a common clinical syndrome in the cardiac intensive care unit with a high mortality rate. Inflammation and oxidative stress have been reported to play a crucial role in the development of ALI. Previous studies have shown that human umbilical cord mesenchymal stem cells (hucMSCs) have anti-inflammatory and antioxidative effects in various diseases. However, the anti-inflammatory and antioxidative effects of the hucMSC conditioned medium (CM) on LPS-induced ALI remain unclear. Therefore, in this study, we assessed whether the hucMSC conditioned medium could attenuate LPS-induced ALI and the underlying mechanisms. Mice were randomly divided into four groups: the control group, PBS group, LPS+PBS group, and LPS+CM group. The lung histopathology and bronchoalveolar lavage fluid (BALF) were analyzed after intervention. The Nrf2/NF-kappaB signaling pathway and its downstream target genes were tested, and the cytokines and growth factors in CM were also measured. The results showed that CM significantly attenuated the histological alterations; decreased the wet/dry weight ratio; reduced the levels of MPO, MDA and ROS; increased SOD and GSH activity; and downregulated the level of proinflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha. Furthermore, CM promoted the expression of Nrf2 and its target genes NQ01, HO-1, and GCLC and inhibited the expression of NF-kappaB and its target genes IL-6, IL-1beta, and TNF-alpha. These effects may be closely related to the large amounts of cytokines and growth factors in the CM. In conclusion, our results demonstrated that CM could attenuate LPS-induced ALI, probably due to inhibition of inflammation and oxidative stress via the Nrf2/NF-kappaB signaling pathway. CI - Copyright (c) 2021 Yue Tang et al. FAU - Tang, Yue AU - Tang Y AD - Department of Cardiothoracic Surgery; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Pediatrics; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, China. FAU - Ding, Fengxia AU - Ding F AD - Chongqing Key Laboratory of Pediatrics; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, China. AD - Department of Respiratory Medicine; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Wu, Chun AU - Wu C AD - Department of Cardiothoracic Surgery; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Liu, Bo AU - Liu B AUID- ORCID: 0000-0001-9918-7749 AD - Department of Cardiothoracic Surgery; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Pediatrics; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20210813 PL - United States TA - Anal Cell Pathol (Amst) JT - Analytical cellular pathology (Amsterdam) JID - 101541993 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 0 (lipopolysaccharide, E coli O55-B5) SB - IM MH - Acute Lung Injury/chemically induced/metabolism/pathology/*prevention & control MH - Animals MH - Anti-Inflammatory Agents/metabolism/pharmacology MH - Antioxidants/metabolism/*pharmacology MH - Cells, Cultured MH - Culture Media, Conditioned/metabolism/*pharmacology MH - Cytokines/genetics/metabolism MH - Disease Models, Animal MH - Gene Expression Regulation MH - Humans MH - Lipopolysaccharides MH - Lung/*drug effects/metabolism/pathology MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/*metabolism MH - NF-kappa B/*metabolism MH - Oxidative Stress/*drug effects MH - Pneumonia/chemically induced/metabolism/pathology/*prevention & control MH - Pulmonary Edema/chemically induced/metabolism/pathology/prevention & control MH - Reactive Oxygen Species/metabolism MH - Signal Transduction MH - Mice PMC - PMC8380155 COIS- All of the authors declared no competing interests. EDAT- 2021/08/25 06:00 MHDA- 2022/02/09 06:00 PMCR- 2021/08/13 CRDT- 2021/08/24 06:22 PHST- 2020/10/28 00:00 [received] PHST- 2021/07/09 00:00 [revised] PHST- 2021/08/03 00:00 [accepted] PHST- 2021/08/24 06:22 [entrez] PHST- 2021/08/25 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/08/13 00:00 [pmc-release] AID - 10.1155/2021/6653681 [doi] PST - epublish SO - Anal Cell Pathol (Amst). 2021 Aug 13;2021:6653681. doi: 10.1155/2021/6653681. eCollection 2021.