PMID- 34059076 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210604 IS - 1476-9255 (Print) IS - 1476-9255 (Electronic) IS - 1476-9255 (Linking) VI - 18 IP - 1 DP - 2021 May 31 TI - Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm. PG - 21 LID - 10.1186/s12950-021-00285-5 [doi] LID - 21 AB - BACKGROUND: Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity. METHODS: M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-gamma and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. RESULTS: The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-gamma induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively. CONCLUSIONS: Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent. FAU - Wang, Shuxia AU - Wang S AUID- ORCID: 0000-0001-9569-8031 AD - Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China. FAU - Xu, Shuhang AU - Xu S AD - Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. FAU - Zhou, Jing AU - Zhou J AD - Department of Pharmaceutical Analysis and Metabolomics, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China. FAU - Zhang, Li AU - Zhang L AD - Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China. FAU - Mao, Xiaodong AU - Mao X AD - Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. FAU - Yao, Xiaoming AU - Yao X AD - Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. yaoxm73@163.com. AD - Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China. yaoxm73@163.com. FAU - Liu, Chao AU - Liu C AD - Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100 Hongshan Road, Nanjing, 210028, China. profliuchao@163.com. LA - eng GR - SLJ0209/Leading Talents Program of Traditional Chinese Medicine of Jiangsu Province/ GR - FY201809/Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education (CN)/ PT - Journal Article DEP - 20210531 PL - England TA - J Inflamm (Lond) JT - Journal of inflammation (London, England) JID - 101232234 PMC - PMC8165957 OTO - NOTNLM OT - Bone marrow-derived macrophage polarisation OT - Cytokines OT - Inflammation OT - Luteolin COIS- The authors declare that they have no competing interests. EDAT- 2021/06/02 06:00 MHDA- 2021/06/02 06:01 PMCR- 2021/05/31 CRDT- 2021/06/01 05:41 PHST- 2020/12/15 00:00 [received] PHST- 2021/05/04 00:00 [accepted] PHST- 2021/06/01 05:41 [entrez] PHST- 2021/06/02 06:00 [pubmed] PHST- 2021/06/02 06:01 [medline] PHST- 2021/05/31 00:00 [pmc-release] AID - 10.1186/s12950-021-00285-5 [pii] AID - 285 [pii] AID - 10.1186/s12950-021-00285-5 [doi] PST - epublish SO - J Inflamm (Lond). 2021 May 31;18(1):21. doi: 10.1186/s12950-021-00285-5.