RvD1 regulates microglial polarization through FPR2 to improve cerebral ischemia-reperfusion injury in rats / 中国药理学通报

Aim To investigate whether RvDl regulates microglial polarization through FPR2 and alleviates the inflammatory damage after cerebral ischemiareperfusion. Methods The middle cerebral artery occlusion (MCAO) model was established by Longa method. The rats after MCAO were randomly divided into; model group, RvD1 group and RvD1 + Boc-2 group, and a sham-operated group was set up as control as well. Cerebral infarct volume was measured, MPO activities in rat brain were measured by immunofluorescence. The expression and localization of FPR2/Iba-1, CD16/Iba-1 and CD206/Iba-1 were detected by immunofluorescence double labeling method. The expressions of TNF-α, IL-1β and iNOS in M1 and TGF-β, IL-10, Arg-1 in M2 were detected by RT-qPCR. Results RvDl significantly reduced cerebral infarction volume and the expression of MPO, and its receptor FPR2 was expressed in microglia. RvD1 down-regulated M1 markers CD16

Polarization of microglia/macrophages and its role in ischemic stroke repair / 中国药理学通报

Traditionally, microglia/macrophage activation is thought to be detrimental in ischemic stroke. However, there is increasing evidence that microglia/macrophage activation is essential for attenuating neuronal apoptosis after cerebral ischemia, promoting neurogenesis and promoting functional recovery. Current research suggests that the inflammatory microenvironment greatly affects the phenotypic changes of microglia/macrophages, so that the same brain tissue has different gene expression patterns and biological functions at different stages of brain damage. This review provides a comprehensive review of the mechanisms of microglia/macrophage activation and the possible potential therapies.

Curcumin induces M1 phenotype derived from murine RAW264.7 macrophages polarization to alternatively activated M2 phenotype / 西安交通大学学报(医学版)

ABSTRACT:Objective To observe the effect of curcumin on RAW264.7 macrophages induced with LPS and IFNγ(M1)and the mechanisms involved.Methods Curcumin of different concentrations (6.25 μmol/L,12.5μmol/L and 25 μmol/L)was used to treat RAW264.7 macrophages induced with LPS and IFNγ(M1)for 12 h,and RAW264.7 macrophages induced with LPS and IFNγ(M1)were incubated with 20μmol/L GW9662 and 25 μmol/L curcumin for 12 h.Using Real-time PCR,ELISA and Western blotting analysis,we examined the expressions of IL-1β,IL-6,PPARγand phenotype markers M2 (KLF4,FIZZ1,and MGL1 )and the expressions of KLF4 and FIZZ1 when PPARγwas inhibited.Results Curcumin of different concentrations all could inhibit the expressions of IL-1βand IL-6 in RAW264.7 macrophages induced with LPS and IFNγ(M1).Curcumin of different concentra-tions could upregulate the expression of M2 markers (KLF4,FIZZ1 and MGL1)and PPARγin RAW264.7 macro-phages induced with LPS and IFNγ(M1).When M1 macrophages were incubated with curcumin and GW9662,the expression of the M2 phenotype markers was reduced.Conclusion Curcumin polarized the M1 phenotype macro-phages derived from RAW264.7 macrophages to become M2 phenotype through activating PPARγ.

Effect of sinomenine on mouse RAW264.7 macrophage cells line polarization induced by LPS or IL-4 / 中国免疫学杂志

Objective:To investigate sinomenine (Sinomenine,SIN) effect on RAW264.7 cells polarization to M1 or M2 phenotype induced by lipopolysaccharide (LPS) or interleukin-4 (IL-4) .Methods:RAW264.7 cells were induced to polarize to M1 by LPS ,and to M2 by IL-4.Sinomenine effects on LPS or IL-4 induced macrophages:TNF-αand IL-10 secretion induced by different condition were detected by Enzyme linked immunosorbent assay (ELISA);The expression level of mRNA of Arginase1(Arg-1),Nitric oxide synthase(iNOS),suppressor of cytokine signaling protein-2(SOCS2) and suppressor of cytokine signaling protein-3(SOCS3) of M1/M2 phenotypes were detected by real time PCR respectively.Results:Sinomenine inhibited the increase of TNF-αsecretion,iNOS and SOCS3 mRNA expression level induced by LPS.Sinomenine inhibited the increase of IL-10 secretion and Arg-1 mRNA expression level induced by IL-4,but SOCS2 mRNA expression level was not affected by Sinomenine.Conclusion: Sinomenine can inhibite the macrophage polarization to M1 and M2 induced by LPS and IL-4.Sinomenine plays a regulatory role on imbalance of M1/M2,and is conducive to maintain the dynamic balance.

Role of Cordycepin and Adenosine on the Phenotypic Switch of Macrophages via Induced Anti-inflammatory Cytokines

BACKGROUND: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. METHODS: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. RESULTS: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin (40 microgram/ml). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-1beta, TNF-alpha) and chemokines (CX3CR1, RANTES), as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-beta) were up-regulated by both cordycepin and adenosine. CONCLUSION: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.