鸢尾素介导抗炎和抗氧化作用的机制

doi:10.3969/j.issn.1004-616x.2022.04.001

Abstract

Abstract: OBJECTIVE: To investigate mechanisms of antioxidant and anti-inflammatory effects mediated by Irisin in mouse macrophages RAW264.7. METHODS: RAW264.7 cells were treated with 200 ng/mL Irisin for 0, 24 and 48 h. Real-time PCR was used to detect mRNA expressions of anti-inflammatory factors (IL-10,Arg-1,and CD206),antioxidant genes (HO-1 and SOD2) and PPAR-γ. ELISA assay was used to detect IL-10, Arg-1 in cell supernatants. Commercial kits were used to determine antioxidant enzyme activities,and Western-blot and immunofluorescence to detect Nrf2 and PPAR-γ expression and localization. Furthermore, after 24 h with 100 ng/mL LPS stimulation of RAW264.7 and 4 h 200 ng/mL Irisin pretreatment, real-time PCR was used to detect pro-inflammatory cytokines. DCFH-DA and Mito-LX were used to detect ROS levels. PPAR-γ inhibitor T0070907 (30 μmol/mL) was pretreated for 4 h and 200 ng/mL Irisin for 24 h, real-time PCR was used to detect expressions of anti-inflammatory cytokines. RESULTS: Compared with the untreated cells,Irisin promoted the expression and release of anti-inflammatory factors such as IL-10, Arg-1 and CD206 (P<0.05). However, Irisin inhibited LPS-induced TNF-α and IL-6 mRNA expression (P<0.05), which indicated that Irisin has anti-inflammatory effects. In addition, Nrf2 nuclear translocation occurred after irisin treatment in RAW264.7 cells. Expressions and enzyme activities of HO-1 and SOD2 were significantly enhanced, and the contents of GSH increased (P<0.05). In response to Irisin stimulation, PPAR-γ expression was elevated and underwent nuclear translocation, while PPAR-γ inhibitor T0070907 blocked the Irisin-induced anti-inflammatory response (P<0.05). CONCLUSION: Irisin initiated macrophage M2-type polarization and anti-inflammatory responses through enhancement of PPAR-γ-related anti-inflammatory genes and Nrf2-related antioxidant enzymes. Therefore,Irisin may be a candidate drug for inflammation-related diseases.

Key words: irisin, macrophage, anti-inflammation, antioxidant, PPAR-γ, Nrf2

CLC Number:

R114

TU Yongmei, YU Weihua, PENG Jie, LIU Jiangzheng, LIU Rui, WU Hao, KONG Deqin, HE Gaihua, LI Wenli, WANG Chong. A mechanistic study on irisin-mediated anti-inflammatory and antioxidant effects in cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(4): 247-254,261.

References

[1] GARLET G P, GIANNOBILE W V.Macrophages:the bridge between inflammation resolution and tissue repair?[J].J Dent Res, 2018, 97(10):1079-1081.
[2] SICA A, ERRENI M, ALLAVENA P, et al.Macrophage polarization in pathology[J].Cell Mol Life Sci, 2015, 72(21):4111-4126.
[3] SHAPOURI-MOGHADDAM A, MOHAMMADIAN S, VAZINI H, et al.Macrophage plasticity, polarization, and function in health and disease[J].J Cell Physiol, 2018, 233(9):6425-6440.
[4] LOCATI M, CURTALE G, MANTOVANI A.Diversity, mechanisms, and significance of macrophage plasticity[J].Annu Rev Pathol, 2020, 15:123-147.
[5] 贾瑞,惠毅,闫曙光,等.巨噬细胞M1/M2型极化与免疫炎症性疾病关系的研究进展[J].中国免疫学杂志, 2021, 37(22):2791-2797.
[6] BOSTRÖM P, WU J, JEDRYCHOWSKI M P, et al.A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J].Nature, 2012, 481(7382):463-468.
[7] JIA S S, YANG Y, BAI Y S, et al.Mechanical stimulation protects against chondrocyte pyroptosis through irisin-induced suppression of PI3K/Akt/NF-κB signal pathway in osteoarthritis[J].Front Cell Dev Biol, 2022, 10:797855.
[8] LIAO W, HE X J, YI Z W, et al.Chelidonine suppresses LPS-Induced production of inflammatory mediators through the inhibitory of the TLR4/NF-κB signaling pathway in RAW_264.7 macrophages[J].Biomed Pharmacother, 2018, 107:1151-1159.
[9] YE W B, WANG J Z, LIN D S, et al.The immunomodulatory role of irisin on osteogenesis via AMPK-mediated macrophage polarization[J].Int J Biol Macromol, 2020, 146:25-35.
[10] WU H M, NI X X, XU Q Y, et al.Regulation of lipid-induced macrophage polarization through modulating peroxisome proliferator-activated receptor-gamma activity affects hepatic lipid metabolism via a Toll-like receptor 4/NF-κB signaling pathway[J].J Gastroenterol Hepatol, 2020, 35(11):1998-2008.
[11] MEDZHITOV R.Origin and physiological roles of inflammation[J].Nature, 2008, 454(7203):428-435.
[12] 刘佳宁,王鑫雅,孙玥.巨噬细胞极化对炎症性疾病影响的研究进展[J].生物化工, 2020, 6(1):112-115.
[13] 许倩,李顺,陈善泽.巨噬细胞极化与炎症性疾病[J].国外医药:抗生素分册, 2018, 39(1):80-85.
[14] ALKHAIRI I, CHERIAN P, ABU-FARHA M, et al.Increased expression of meteorin-like hormone in type 2 diabetes and obesity and its association with irisin[J].Cells, 2019, 8(10):1283.
[15] IRANDOOST P, MESRI ALAMDARI N, SAIDPOUR A, et al.The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats[J].J Food Biochem, 2020, 44(12):e13493.
[16] XIONG X Q, GENG Z, ZHOU B, et al.FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPKmediated macrophage polarization in obesity[J].Metabolism, 2018, 83:31-41.
[17] XIN T, LU C Z.Irisin activates Opa1-induced mitophagy to protect cardiomyocytes against apoptosis following myocardial infarction[J].Aging, 2020, 12(5):4474-4488.
[18] DE MIGUEL Z, KHOURY N, BETLEY M J, et al.Exercise plasma boosts memory and dampens brain inflammation via clusterin[J].Nature, 2021, 600(7889):494-499.
[19] BRÜNE B, DEHNE N, GROSSMANN N, et al.Redox control of inflammation in macrophages[J].Antioxid Redox Signal, 2013, 19(6):595-637.
[20] SINGLA B, HOLMDAHL R, CSANYI G.Editorial:oxidants and redox signaling in inflammation[J].Front Immunol, 2019, 10:545.
[21] KRATZ M, COATS B R, HISERT K B, et al.Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages[J].Cell Metab, 2014, 20(4):614-625.
[22] CHOI M J, LEE E J, PARK J S, et al.Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia:critical role of PPAR-γ signaling pathway[J].Biochem Pharmacol, 2017, 144:120-131.
[23] GAO S S, ZHOU J, LIU N, et al.Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13[J].J Mol Cell Cardiol, 2015, 85:131-139.
[24] LIN C, GUO Y Z, XIA Y L, et al.FNDC5/Irisin attenuates diabetic cardiomyopathy in a type 2 diabetes mouse model by activation of integrin αV/β5-AKT signaling and reduction of oxidative/nitrosative stress[J].J Mol Cell Cardiol, 2021, 160:27-41.
[25] 于卫华,孔德钦,龙子,等.抗氧化悖论真的成立吗?[J].癌变·畸变·突变, 2021, 33(5):388-392.

A mechanistic study on irisin-mediated anti-inflammatory and antioxidant effects in cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	ZHAO Chenqian, XU Anqi, AI Duo, KONG Deqin, ZHANG Xiaodi, LI Wenli, HAI Chunxu, LIU Jiangzheng. Effects of Mito-TEMPO treatment on nitrogen mustard-induced cytotoxicity in BEAS-2B cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(3): 161-168.
[2]	ZHANG Zihan, LI Li, ZHANG Wenfeng, ZHANG Yanchao, CHEN Huiling, SHI Ming. Effects of triphenyl phosphate ontoxicity and phagocytosis of mouse macrophage RAW264.7 [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 269-275.
[3]	CHEN Tingyu, CHEN Dayin, XIE Jinlu, GAO Xiren, LU Chunfeng. Role of the Nrf2/ARE signaling pathway on quercetin-inhibition of INH-induced mitochondrial oxidative damage in hepatocytes [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 208-212,217.
[4]	CHEN Zizhuo, XU Yuhang, JIANG Xiaoxu, ZHAO Jiuzhou, ZHU Jingpu, ZHENG Yipeng, WU Haozhi, LI Wenli, WANG Xin, HAI Chunxu, YU Weihua. Inhibition of LPS-induced inflammatory response by butein in bone marrow primary macrophages [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 171-176.
[5]	CHEN Zizhuo, XU Yuhang, ZHAO Jiuzhou, ZHU Jingpu, ZHENG Yipeng, LI Wenli, WU Haozhi, HAI Chunxu, YU Weihua. Antioxidant and anti-inflammatory effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in macrophages [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 105-111,117.
[6]	HAN Hedan, WANG Hai, LI Ailin, HAN Zhaoyu, GAO Liping. Protective effect of Rhodiola extract on cisplatin-induced nephrotoxicity [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(3): 204-208.
[7]	HAN Hedan, WANG Hai, GAO Liping. Protective effects of allicin on cisplatin-induced toxicity in HEK293 kidney cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(1): 20-24.
[8]	WANG Hai, LIAN Yanna, GAO Liping, QU Lijie, ZHANG Dongping. Effect of catechin on cisplatin-induced oxidative damage in human embryonic kidney cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(1): 51-54.
[9]	LI Yifeng, YAN Dong, HE Yingxue, JIANG Xiaoyan, DING Kuke. Some physiological effects of strontium on hydroponic Chinese cabbage and rape [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(3): 223-226.
[10]	ZHENG Zhijia, TIAN Jinglin, MEI Shujiang, LIN Guimiao, WANG Xiaomei, ZHU Xuedan, TANG Jie, ZHANG Ke, CHEN Xianxiong. Effects of InP/ZnS quantum dots on function of mouse macrophage cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(1): 19-22.
[11]	FANG Congwen, BAI Hua, ZHANG Xiaodi, LIU Rui, HAI Chunxu. Protective effects of maize silks ethanol extract on oxidative injury in L929 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(6): 426-431.
[12]	LIU Ying, FU Han, SHI Tengrui, LIU Jiangzheng, WANG Xin, HAI Chunxu. Effect of high fat diet on oxidative stress and protein expressions of Nrf2, NRF-1 and mtTFA in liver of C57 mice during hepatic insulin resistance [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(3): 191-196.
[13]	ZHANG Jun，KONG Jie，ZHANG An-du，KONG De-you，ZHANG Jian. The relationship between the expression and clinical significance of Nrf2 and Bcl-2 in esophageal squamous cell carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2014, 26(6): 419-422.
[14]	QIN Xu-jun，HE Wei，HAI Chun-xu*. Role of protein Bcl-2 in the oxidative injury induced by radiotherapy or chemotherapy [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2014, 26(5): 361-364.
[15]	PENG Jie，LI Yu-liang，WU Hao，LIANG Xin，HAI Chun-xu. Protective effects of ligustrazine against oxidative stress induced by irradiation in mice [J]. , 2012, 24(3): 231-234.