scholarly journals Curcumin Alleviated Dextran Sulfate Sodium-Induced Colitis by Regulating M1/M2 Macrophage Polarization and TLRs Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zeng-Ping Kang ◽  
Meng-Xue Wang ◽  
Tian-Tian Wu ◽  
Duan-Yong Liu ◽  
Hai-Yan Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Macrophage Polarization ◽  
Experimental Colitis ◽  
The Body ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
M2 Macrophage Polarization

Curcumin has shown good efficacy in mice with experimental colitis and in patients with ulcerative colitis, but the mechanism of action through the regulation of M1/M2 macrophage polarization has not been elaborated. The ulcerative colitis was modeled by dextran sulfate sodium; colitis mice were orally administrated with curcumin (10 mg/kg/day) or 5-ASA (300 mg/kg/day) for 14 consecutive days. After curcumin treatment, the body weight, colon weight and length, colonic weight index, and histopathological damage in colitis mice were effectively improved. The concentrations of proinflammatory cytokines IL-1β, IL-6, and CCL-2 in the colonic tissues of colitis mice decreased significantly, while anti-inflammatory cytokines IL-33 and IL-10 increased significantly. Importantly, macrophage activation was suppressed and M1/M2 macrophage polarization was regulated in colitis mice, and the percentage of CD11b+F4/80+ and CD11b+F4/80+TIM-1+ and CD11b+F4/80+iNOS+ decreased significantly and CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ increased significantly. Additionally, curcumin significantly downregulated CD11b+F4/80+TLR4+ macrophages and the protein levels of TLR2, TLR4, MyD88, NF-κBp65, p38MAPK, and AP-1 in colitis mice. Our study suggested that curcumin exerted therapeutic effects in colitis mice by regulating the balance of M1/M2 macrophage polarization and TLRs signaling pathway.

scholarly journals DA-DRD5 signaling controls colitis by regulating colonic M1/M2 macrophage polarization

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Lu Liu ◽  
Yuqing Wu ◽  
Bingwei Wang ◽  
Yuying Jiang ◽  
Lin Lin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Macrophage Polarization ◽  
Experimental Colitis ◽  
M2 Macrophage ◽  
M1 Macrophages ◽  
Inflammatory Bowel ◽  
M2 Macrophage Polarization ◽  
Mechanistic Basis ◽  
Functional Relevance ◽  
Creb Pathway

AbstractThe decrease of neurotransmitter dopamine (DA) levels in the intestine is closely related to the development of inflammatory bowel disease (IBD). However, the functional relevance and underlying mechanistic basis of the effects of DA signaling on IBD remains unclear. Here, we observed that the DRD5 receptor is highly expressed in colonic macrophages, and the deficiency of DA-DRD5 signaling exacerbated experimental colitis. Moreover, DA-DRD5 signaling can inhibit M1 by negatively regulating NF-κB signaling but promote M2 macrophage polarization through activation of the CREB pathway, respectively. The deficiency of DRD5 signaling increased colonic M1 macrophages but reduced M2 cells during colitis. Additionally, the administration of a D1-like agonist that has a higher affinity to DRD5 can attenuate the colitogenic phenotype of mice. Collectively, these findings provide the first demonstration of DA-DRD5 signaling in colonic macrophages controlling the development of colitis by regulating M1/M2 macrophage polarization.

scholarly journals Convallatoxin Promotes M2 Macrophage Polarization to Attenuate Atherosclerosis Through PPARγ-Integrin αvβ5 Signaling Pathway

2021 ◽  
Vol Volume 15 ◽  
pp. 803-812
Author(s):  
Yi Zhang ◽  
Xiujin Shi ◽  
Jialun Han ◽  
Wenxing Peng ◽  
Zhenwei Fang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization

scholarly journals Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis

2021 ◽  
Author(s):  
Hogjuan Ning ◽  
Haixu Chen ◽  
Jingyu Deng ◽  
Chun Xiao ◽  
Lina Shan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathway ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
Cell Based Therapy ◽  
Anti Inflammation

Abstract Background Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secreted more exosomes, but little was known on MI repair. Methods Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis, and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs–Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF-κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

scholarly journals Cinacalcet Targets the Neurokinin-1 Receptor and Inhibits PKCδ/ERK/P65 Signaling to Alleviate Dextran Sulfate Sodium-Induced Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuehong Chen ◽  
Huan Liu ◽  
Qiuping Zhang ◽  
Yubin Luo ◽  
Liang Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Structural Integrity ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Therapeutic Effects ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Objective: Inflammatory bowel disease is an immune-mediated chronic inflammatory disease of the gastrointestinal tract for which curative drugs are currently not available. This study was performed to assess the therapeutic effects of cinacalcet on dextran sulfate sodium (DSS)-induced colitis.Methods: Primary macrophages obtained from bone marrow and the macrophage cell line RAW264.7 were used to examine the inhibitory effect of cinacalcet on cytokine production, the PKCδ/ERK/P65 signaling pathway, and NF-κB P65 translocation. Colitis was induced using DSS to assess the treatment effect of cinacalcet. Bioinformatics approaches were adopted to predict potential targets of cinacalcet, and a drug affinity responsive target stability (DARTs) assay was performed to confirm binding between cinacalcet and potential target.Results:In vivo analysis showed that cinacalcet reduced the disease activity score, prevented shortening of the colon, diminished inflammatory cell infiltration, and protected the structural integrity of the intestinal wall. Cinacalcet also reduced production of the inflammatory cytokines TNFα, IL-1β, and IL-6 in the colon and sera of mice with DSS-induced colitis. In vitro studies revealed that cinacalcet suppressed the translocation of P65 and inhibited production of the inflammatory cytokines IL-1β and IL-6. Mechanistic studies revealed that the target of cinacalcet was neurokinin-1 receptor (NK1R) and their binding was confirmed by a DARTs assay. Furthermore, the inhibition of NK-κB P65 activation was found to occur via the suppression of PKCδ/ERK/P65 signaling mediated by cinacalcet.Conclusion: Cinacalcet inhibits the activation of NF-κB and reduces the production of inflammatory cytokines by suppressing the PKCδ/ERK/P65 signaling pathway via targeting NK1R, suggesting that it can be used to treat inflammatory diseases, particularly colitis.

scholarly journals IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization

Theranostics ◽  
2020 ◽  
Vol 10 (17) ◽  
pp. 7697-7709
Author(s):  
Xiaocang Cao ◽  
Liyun Duan ◽  
Huixing Hou ◽  
Yue Liu ◽  
Shang Chen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
M2 Macrophage Polarization

scholarly journals Is dextran sulfate sodium a good inducer of acute experimental enteritis?

2019 ◽  
Vol 33 ◽  
pp. 205873841984336
Author(s):  
Wei Chen ◽  
Jing Zhang ◽  
Chen Li ◽  
Quan Pan ◽  
Jingtong Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Experimental Colitis ◽  
The Body ◽  
Control Group ◽  
Average Weight ◽  
Inflammatory Infiltration ◽  
Intestine Length ◽  
Hematoxylin And Eosin

Animal models play critical roles in exploring the pathogenesis of human diseases and designing novel therapeutic schemes. Acute experimental colitis (AEC) models have been reported to be established in mice principally by oral administration of dextran sulfate sodium (DSS). However, little knowledge is known about whether DSS can be used to induce the acute experimental enteritis (AEE). In this study, different concentrations of DSS (0%, 2%, 3%, and 5%) were used to induce AEC and AEE models in two cohorts. After the establishment of these two models, the symptoms of the mice induced by DSS were noted, the length and average weight of each colon and small intestine were measured, and hematoxylin and eosin (HE) staining was conducted for assessing the inflammatory infiltration in these models. Generally, the comparison of the inflammatory scoring between AEC and AEE models was analyzed. As a consequence, we found that, the mice with 2%–5% DSS administration in a week could develop into AEC models in two cohorts and AEE models in one cohort, followed by the signs of diarrhea, gross rectal bleeding, weight loss of the body, and shortened colon and intestine length, as compared with the control group. HE staining showed that the inflammatory scoring was dramatically increased by 3%–5% DSS in AEC models in two cohorts but slightly elevated in AEE models in one cohort. Meanwhile, as compared with the severe AEC models, the extent of inflammatory infiltration induced by 3%–5% DSS in AEE models was much milder. In conclusion, oral administration of 3%–5% DSS is a good inducer of AEC models, but not AEE models.

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