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 MiR-98-5p expression inhibits polarization of macrophages to an M2 phenotype by targeting Trib1 in inflammatory bowel disease

2020 ◽  
Author(s):  
Yunhua Peng ◽  
Qingyuan Wang ◽  
Wei Yang ◽  
Qiqi Yang ◽  
Ynani Pei ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Macrophage Polarization ◽  
Luciferase Reporter ◽  
Marker Genes ◽  
M2 Macrophage ◽  
M1 Macrophage ◽  
Inflammatory Bowel ◽  
M2 Macrophage Polarization ◽  
M2 Phenotype

Herein, we unfolded miR-98-5p mechanism in inflammatory bowel disease (IBD). IBD mouse model was established. The severity of colitis was assessed daily using the disease activity index (DAI). Murine peritoneal macrophages were stimulated by lipopolysaccharide (LPS). MiR-98-5p, tribbles homolog 1 (Trib1), M1 and M2 macrophage marker genes mRNA expression was analyzed. The relationship between miR-98-5p and Trib1 was explored using a luciferase reporter assay. The strategy of loss-of-function was used to explore the mechanism of miR-98-5p in macrophage polarization, inflammation and IBD. The results revealed that IBD mice had higher DAI index and miR-98-5p expression when compared to the Sham group. MiR-98-5p and Trib1 displayed a targeted regulation relationship. Knockdown of miR-98-5p transformed LPS-induced M1 macrophage polarization into M2 macrophage polarization and inhibited inflammation via up-regulating Trib1. However, shTrib1 reversed the effects. In vivo experiment, silencing of miR-98-5p, diminished the DAI and promoted M2 macrophage polarization. In conclusion, knockdown of miR-98-5p changed macrophage polarization to the M2 phenotype by increasing Trib1 expression, thereby alleviating IBD symptoms.

scholarly journals YAP Aggravates Inflammatory Bowel Disease by Regulating M1/M2 Macrophage Polarization and Gut Microbial Homeostasis

Cell Reports ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 1176-1189.e5 ◽  
Author(s):  
Xin Zhou ◽  
Weiyun Li ◽  
Shuang Wang ◽  
Panli Zhang ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Inflammatory Bowel ◽  
M2 Macrophage Polarization

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 M2 macrophage polarization in chronic spontaneous urticaria refractory to antihistamine treatment

2021 ◽  
Author(s):  
Roberta F.J. Criado ◽  
Paulo Ricardo Criado ◽  
Carla Pagliari ◽  
Mirian N. Sotto ◽  
Carlos D'Apparecida Machado Filho ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Chronic Spontaneous Urticaria ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization

Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

2021 ◽  
pp. 107424842198957
Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Heart Function ◽  
Macrophage Polarization ◽  
Late Phase ◽  
Macrophage Infiltration ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

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