PMID- 35748972 OWN - NLM STAT- MEDLINE DCOM- 20220713 LR - 20240410 IS - 1573-4978 (Electronic) IS - 0301-4851 (Print) IS - 0301-4851 (Linking) VI - 49 IP - 7 DP - 2022 Jul TI - IL35 attenuated LPS-induced acute lung injury by regulating macrophage polarization. PG - 5811-5820 LID - 10.1007/s11033-022-07293-5 [doi] AB - BACKGROUND: Interleukin 35 (IL35) has been reported to play a role in acute lung injury (ALI); however, the current results regarding the relationship between IL35 and ALI are inconsistent. Therefore, we aimed to further determine the function of IL35 in ALI in mice and the potential mechanism in this paper. MATERIALS AND METHODS: Hematoxylin-eosin (HE) staining and Masson staining were used to evaluate lung injury in mice. Immunohistochemical staining was used to evaluate the expression of IL35 p35, TLR4 and MD2 and the Bax/Bcl2 and p-P65/P65 ratios. The expression levels of IL35 EBi3, CD68, CD206 and MPO were assessed by immunofluorescence staining. RT-PCR was used to examine the expression levels of IL1beta and IL6. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect apoptotic cells. RESULTS: Overexpression of IL35 alleviated LPS-induced ALI in mice. IL35 overexpression decreased the expression of CD68 and increased the expression of CD206 in mice with ALI. Furthermore, upregulation of IL35 expression obviously reduced the expression of MPO, IL1beta and IL6 in the lung tissues of mice with ALI. Mechanistically, IL35 suppressed the TLR4/NFkappaB-P65 pathway, leading to the promotion of the M1 to M2 macrophage transition and alleviation of inflammation in mice with ALI. CONCLUSIONS: IL35 relieved LPS-induced inflammation and ALI in mice by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NFkappaB-P65 pathway. CI - (c) 2022. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Chen, Shengsong AU - Chen S AUID- ORCID: 0000-0003-2763-943X AD - Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, No 9, Dongdan Santao, Dongcheng District, 100730, Beijing, P. R. China. AD - National Center for Respiratory Medicine, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - National Clinical Research Center for Respiratory Diseases, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. FAU - Xia, Jingen AU - Xia J AD - Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - National Center for Respiratory Medicine, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - National Clinical Research Center for Respiratory Diseases, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. AD - WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. FAU - Zhang, Yi AU - Zhang Y AD - Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. czzhangyi1985@126.com. AD - National Center for Respiratory Medicine, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. czzhangyi1985@126.com. AD - Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. czzhangyi1985@126.com. AD - National Clinical Research Center for Respiratory Diseases, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. czzhangyi1985@126.com. AD - WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. czzhangyi1985@126.com. FAU - Zhan, Qingyuan AU - Zhan Q AD - Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. drzhanqy@163.com. AD - Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, No 9, Dongdan Santao, Dongcheng District, 100730, Beijing, P. R. China. drzhanqy@163.com. AD - National Center for Respiratory Medicine, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. drzhanqy@163.com. AD - Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. drzhanqy@163.com. AD - National Clinical Research Center for Respiratory Diseases, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. drzhanqy@163.com. AD - WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China. drzhanqy@163.com. LA - eng GR - 81870072/the National Natural Science Foundation of China/ PT - Journal Article DEP - 20220624 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Interleukin-6) RN - 0 (Interleukins) RN - 0 (Lipopolysaccharides) RN - 0 (Toll-Like Receptor 4) SB - IM MH - *Acute Lung Injury/chemically induced/metabolism MH - Animals MH - Inflammation MH - Interleukin-6 MH - Interleukins/genetics MH - *Lipopolysaccharides MH - Lung/metabolism MH - Macrophages/metabolism MH - Mice MH - Toll-Like Receptor 4/genetics/metabolism PMC - PMC9244303 OTO - NOTNLM OT - Acute lung injury OT - Inflammation OT - Interleukin 35 OT - Macrophage polarization COIS- All the authors declare no confict of interest. EDAT- 2022/06/25 06:00 MHDA- 2022/07/14 06:00 PMCR- 2022/06/30 CRDT- 2022/06/24 11:17 PHST- 2021/12/06 00:00 [received] PHST- 2022/02/23 00:00 [accepted] PHST- 2022/01/27 00:00 [revised] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/06/24 11:17 [entrez] PHST- 2022/06/30 00:00 [pmc-release] AID - 10.1007/s11033-022-07293-5 [pii] AID - 7293 [pii] AID - 10.1007/s11033-022-07293-5 [doi] PST - ppublish SO - Mol Biol Rep. 2022 Jul;49(7):5811-5820. doi: 10.1007/s11033-022-07293-5. Epub 2022 Jun 24.