PMID- 36902060 OWN - NLM STAT- MEDLINE DCOM- 20230410 LR - 20230410 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 5 DP - 2023 Feb 27 TI - Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide. LID - 10.3390/ijms24054629 [doi] LID - 4629 AB - Isocorydine (ICD) is a type of isoquinoline alkaloid originating from Corydalis edulis, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-kappaB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury. FAU - Tu, Yifan AU - Tu Y AD - Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China. AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Li, Xiaodong AU - Li X AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Fu, Yuanzheng AU - Fu Y AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Chen, Yunyun AU - Chen Y AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Fang, Hui AU - Fang H AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Li, Yuan AU - Li Y AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Gu, Ying AU - Gu Y AD - Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China. AD - Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. FAU - Zhang, Jiawei AU - Zhang J AD - Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China. LA - eng GR - 32070630/National Natural Science Foundation of China/ GR - 32100477/National Natural Science Foundation of China/ GR - 2019KY574/Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ GR - 2020R01006/the Zhejiang Innovation Team Grant/ PT - Journal Article DEP - 20230227 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Interleukin-6) RN - 3B5E87JEOX (isocorydine) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Aporphines) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) SB - IM MH - Animals MH - Mice MH - *Acute Lung Injury/metabolism MH - *Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung/pathology MH - Macrophages/metabolism MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - *Aporphines/pharmacology MH - *Anti-Inflammatory Agents, Non-Steroidal/pharmacology PMC - PMC10003757 OTO - NOTNLM OT - acute lung injury OT - interleukin-6 OT - isocorydine OT - lipopolysaccharide OT - macrophages COIS- The authors declare no conflict of interest. EDAT- 2023/03/12 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/02/27 CRDT- 2023/03/11 01:17 PHST- 2022/12/17 00:00 [received] PHST- 2023/02/16 00:00 [revised] PHST- 2023/02/22 00:00 [accepted] PHST- 2023/03/11 01:17 [entrez] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/02/27 00:00 [pmc-release] AID - ijms24054629 [pii] AID - ijms-24-04629 [pii] AID - 10.3390/ijms24054629 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 27;24(5):4629. doi: 10.3390/ijms24054629.