Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Ding, Ning; Wang, Yuxing; Dou, Ce; Liu, Feila; Guan, Ge; Wei, Keyu; Yang, Jingyuan; Yang, Mingcan; Tan, Ju; Zeng, Wen; Zhu, Chuhong

doi:10.1002/jcp.27537

Cited by 67 publications

(41 citation statements)

References 55 publications

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“…Herbal compound Physalin D can repolarize M1 toward M2 polarization in BMDM through STAT1 suppression and STAT6 activation (29), which consist with our study.…”

Section: Genessupporting

confidence: 90%

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Wang¹,

Cao

et al. 2020

Preprint

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ABSTRACTMacrophage are indispensable regulator cells in inflammatory response. Macrophage polarization and its secreted inflammatory factors have affinity with the outcomes of inflammation. Luteolin, a flavonoid abundant in plants has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarization of BMDM to suppress inflammation is still veiled. The purpose of this study was to observe the effects of luterolin on the polarity of BMDM derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism of luteolin regulating the BMDM polarity. M1-polarized BMDM were induced by LPS+IFN-γ, M2-polarization were stimulated with IL-4. BMDM morphology was observed by laser confocal microscopy; levels of BMDM differentiation and CD11c or CD206 on membrane surface were assessed by FCM; mRNA and protein of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. The isolated mouse bone marrow cells were successfully differentiated into BMDM, LPS+IFN-γ induced BMDM M1-phenotype polarization, and IL-4 induced its M2-phenotype polarization. After M1-polarized BMDM treated with luteolin, M1-type pro-inflammatory factors including IL-6, TNF-α□iNOS, CD86 were down-regulated while M2-type anti-inflammatory factors including IL-10, Arg1, CD206 were up-regulated; the expression of M1-type surface marker CD11c decreased, nevertheless, M2-type marker CD206 increased; levels of inflammatory signaling protein p-STAT1 and p-STAT6 were attenuated and enhanced respectively. Our study suggests luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin hold promise as an anti-inflammatory and immunomodulatory agent.

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“…Herbal compound Physalin D can repolarize M1 toward M2 polarization in BMDM through STAT1 suppression and STAT6 activation (29), which consist with our study.…”

Section: Genessupporting

confidence: 90%

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Wang¹,

Cao

et al. 2020

Preprint

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show abstract

“…Moreover, anti-inflammatory, antimalarial, and antinociceptive effects of physalins have been reported (10)(11)(12). We also previously reported that Physalin D can regulate macrophage polarization towards a M2 phenotype (13). However, the effects of physalin in the skeletal system have not been reported, whereas that physalin was suppressive in macrophage activation has been (7).…”

Section: Introductionmentioning

confidence: 97%

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

Ding

Cui

et al. 2020

BMB Rep.

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We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor B ligand (RANKL). The biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Afterwards, we tested cell viability and cell apoptosis rate to analyze the cytotoxicity of different physalins. We analyzed the inhibitory effects of physalins on RANKL-induced osteoclastogenesis from mouse bone-marrow macrophages (BMMs) using a tartrate-resistant acid phosphatase (TRAP) stain. We found that physalin D has the best selectivity index (SI) among all analyzed physalins. We then confirmed the inhibitory effects of physalin D on osteoclast maturation and function by immunostaining of F-actin and a pit-formation assay. On the molecular level, physalin D attenuated RANKLevoked intracellular calcium ([Ca(2＋)](i)) oscillation by inhibiting phosphorylation of phospholipase C2 (PLC2) and thus blocked the downstream activation of Ca2＋/calmodulindependent protein kinases (CaMK)IV and cAMP-responsive element-binding protein (CREB). An animal study showed that physalin D treatment rescues bone microarchitecture, prevents bone loss, and restores bone strength in a model of rapid bone loss induced by soluble RANKL. Taken together, these results suggest that physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via suppressing the PLC2-CaMK-CREB pathway. [BMB Reports 2020; 53(3): 154-159] BMB Rep. 2020; 53(3): 154-159 www.bmbreports.org 157 http://bmbreports.org BMB Reports

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“…In human primary macrophages derived from CD14 + PBMCs, poly (ADP-ribose) polymerase family member 14 (PARP14) silencing accelerated IFNγ induced STAT1 phosphorylation and improved M1 macrophage activation [58]. Ning Ding et al indicated that STAT1 is an important transcription factor for M1 polarization, and identified that physalin D could inhibit M1 polarization by suppressing STAT1 activation [59]. However, the role of STAT1 in upregulated M1 polarization in RSA and the underlying mechanism are still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization

Zhu¹,

Li²,

Zhang³

et al. 2020

Int. J. Biol. Sci.

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Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear. MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated. In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derived M1 macrophages upon IFNγ and LPS stimulation. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1. Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects. Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa. miR-103 regulated STAT1 expression by direct binding to its 3'-UTR. Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively. Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway. miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.

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Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Cited by 67 publications

References 55 publications

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling

MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization

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