Tumor necrosis factor-α-induced protein 8-like-2 is involved in the activation of macrophages by Astragalus polysaccharides in vitro

Zhu,Jie; Zhang,Yuanyuan; Fan,Fanghua; Wu,Guoyou; Xiao,Zhen; Zhou,Huanqin

doi:10.3892/mmr.2018.8730

Tumor necrosis factor-α-induced protein 8-like-2 is involved in the activation of macrophages by Astragalus polysaccharides in vitro

Authors:
- Jie Zhu
- Yuanyuan Zhang
- Fanghua Fan
- Guoyou Wu
- Zhen Xiao
- Huanqin Zhou
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Affiliations: Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China, Department of Pulmonology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China
Published online on: March 13, 2018 https://doi.org/10.3892/mmr.2018.8730
Pages: 7428-7434

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Abstract

In previous years, studies have shown that Astragalus polysaccharides (APS) can improve cellular immunity and humoral immune function, which has become a focus of investigations. Tumor necrosis factor‑α‑induced protein 8‑like 2 (TIPE2) is a negative regulator of immune reactions. However, the effect and underlying mechanisms of TIPE2 on the APS‑induced immune response remains to be fully elucidated. The present study aimed to examine the role of TIPE2 and its underlying mechanisms in the APS‑induced immune response. The production of nitric oxide (NO) was detected in macrophages in vitro following APS stimulation. In addition, the present study interfered with the expression of TIPE2 in macrophages, and examined the production of cytokines, NO and components of the mitogen‑activate protein kinase (MAPK) signaling pathway following APS stimulation. The results showed that APS was able to activate macrophages by inducing the production of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑6 and NO. Furthermore, RAW264.7 cells were stimulated with APS when TIPE2 was silenced, and it was found that the production of TNF‑α, IL‑6, IL‑1β and NO were upregulated, and the signaling pathway of MAPK was activated. Taken together, these results demonstrated that TIPE2 had an important negative effect on the APS‑induced production of inflammatory cytokines and NO via the MAPK signaling pathway.

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1	Ma H, Liu G, Ding W, Wu Y, Cai L and Zhao Y: Diabetes-induced alteration of F4/80+ macrophages: A study in mice with streptozotocin-induced diabetes for a long term. J Mol Med (Berl). 86:391–400. 2008. View Article : Google Scholar : PubMed/NCBI
2	Marcato LG, Ferlini AP, Bonfim RC, Ramos-Jorge ML, Ropert C, Afonso LF, Vieira LQ and Sobrinho AP: The role of Toll-like receptors 2 and 4 on reactive oxygen species and nitric oxide production by macrophage cells stimulated with root canal pathogens. Oral Microbiol Immunol. 23:353–359. 2008. View Article : Google Scholar : PubMed/NCBI
3	Xie C, Kang J, Ferguson ME, Nagarajan S, Badger TM and Wu X: Blueberries reduce pro-inflammatory cytokine TNF-α and IL-6 production in mouse macrophages by inhibiting NF-κB activation and the MAPK pathway. Mol Nutr Food Res. 55:1587–1591. 2011. View Article : Google Scholar : PubMed/NCBI
4	Chu X, Ci X, He J, Wei M, Yang X, Cao Q, Li H, Guan S, Deng Y, Pang D and Deng X: A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the ERK/MAPK signaling pathway. Molecules. 16:7634–7648. 2011. View Article : Google Scholar : PubMed/NCBI
5	Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, et al: TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 133:415–426. 2008. View Article : Google Scholar : PubMed/NCBI
6	Wei W, Xiao HT, Bao WR, Ma DL, Leung CH, Han XQ, Ko CH, Lau CB, Wong CK, Fung KP, et al: TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells. J Ethnopharmacol. 179:243–252. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zhang WJ and Frei B: Astragaloside IV inhibits NF-κB activation and inflammatory gene expression in LPS-treated mice. Mediators Inflamm. 2015:2743142015. View Article : Google Scholar : PubMed/NCBI
8	Denzler KL, Waters R, Jacobs BL, Rochon Y and Langland JO: Regulation of inflammatory gene expression in PBMCs by immunostimulatory botanicals. PLoS One. 5:e125612010. View Article : Google Scholar : PubMed/NCBI
9	Cheng YW, Chang CY, Lin KL, Hu CM, Lin CH and Kang JJ: Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling. J Ethnopharmacol. 120:264–271. 2008. View Article : Google Scholar : PubMed/NCBI
10	Meyer KA, Neeley CK, Baker NA, Washabaugh AR, Flesher CG, Nelson BS, Frankel TL, Lumeng CN, Lyssiotis CA, Wynn ML, et al: Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer. Biochem Biophys Rep. 7:144–149. 2016.PubMed/NCBI
11	Kallon S, Li X, Ji J, Chen C, Xi Q, Chang S, Xue C, Ma J, Xie Q and Zhang Y: Astragalus polysaccharide enhances immunity and inhibits H9N2 avian influenza virus in vitro and in vivo. J Anim Sci Biotechnol. 4:222013. View Article : Google Scholar : PubMed/NCBI
12	Li J, Zhong Y, Li H, Zhang N, Ma W, Cheng G, Liu F, Liu F and Xu J: Enhancement of Astragalus polysaccharide on the immune responses in pigs inoculated with foot-and-mouth disease virus vaccine. Int J Biol Macromol. 49:362–368. 2011. View Article : Google Scholar : PubMed/NCBI
13	Abdullahi AY, Kallon S, Yu X, Zhang Y and Li G: Vaccination with astragalus and ginseng polysaccharides improves immune response of chickens against H5N1 avian influenza virus. Biomed Res Int. 2016:15102642016. View Article : Google Scholar : PubMed/NCBI
14	Jiao L, Li X, Li T, Jiang P and Zhang L, Wu M and Zhang L: Characterization and anti-tumor activity of alkali-extracted polysaccharide from Enteromorpha intestinalis. Int Immunopharmacol. 9:324–329. 2009. View Article : Google Scholar : PubMed/NCBI
15	Palmer RM, Ashton DS and Moncada S: Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 333:664–666. 1988. View Article : Google Scholar : PubMed/NCBI
16	Lejeune FJ, Liénard D, Matter M and Rüegg C: Efficiency of recombinant human TNF in human cancer therapy. Cancer Immun. 6:62006.PubMed/NCBI
17	Park JY, Chung TW, Jeong YJ, Kwak CH, Ha SH, Kwon KM, Abekura F, Cho SH, Lee YC, Ha KT, et al: Ascofuranone inhibits lipopolysaccharide-induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophages. PLoS One. 12:e01713222017. View Article : Google Scholar : PubMed/NCBI
18	Fan YC, Wang N, Sun YY, Xiao XY and Wang K: TIPE2 mRNA level in PBMCs serves as a novel biomarker for predicting short-term mortality of acute-on-chronic hepatitis B liver failure: A prospective single-center study. Medicine (Baltimore). 94:e16382015. View Article : Google Scholar : PubMed/NCBI
19	Xi W, Hu Y, Liu Y, Zhang J, Wang L, Lou Y, Qu Z, Cui J, Zhang G, Liang X, et al: Roles of TIPE2 in hepatitis B virus induced hepatic inflammation in humans and mice. Mol Immunol. 48:1203–1208. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kong L, Liu K, Zhang YZ, Jin M, Wu BR, Wang WZ, Li W, Nan YM and Chen YH: Downregulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with chronic hepatitis C. Hepatol Int. 7:844–849. 2013. View Article : Google Scholar : PubMed/NCBI
21	Li D, Song L, Fan Y, Li X, Li Y, Chen J, Zhu F, Guo C, Shi Y and Zhang L: Down-regulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Immunol. 133:422–427. 2009. View Article : Google Scholar : PubMed/NCBI
22	Lou Y, Sun H, Morrissey S, Porturas T, Liu S, Hua X and Chen YH: Critical roles of TIPE2 protein in murine experimental colitis. J Immunol. 193:1064–1070. 2014. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Wei X, Liu L, Liu S, Wang Z, Zhang B, Fan B, Yang F, Huang S, Jiang F, et al: TIPE2, a novel regulator of immunity, protects against experimental stroke. J Biol Chem. 287:32546–32555. 2012. View Article : Google Scholar : PubMed/NCBI
24	Liu MW, Liu R, Wu HY, Zhang W, Xia J, Dong MN, Yu W, Wang Q, Xie FM, Wang R, et al: Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasingTIPE2 expression. Int J Mol Med. 38:1419–1432. 2016. View Article : Google Scholar : PubMed/NCBI
25	Zhang H, Zhu T, Liu W, Qu X, Chen Y, Ren P, Wang Z, Wei X, Zhang Y and Yi F: TIPE2 acts as a negative regulator linking NOD2 and inflammatory responses in myocardial ischemia/reperfusion injury. J Mol Med (Berl). 93:1033–1043. 2015. View Article : Google Scholar : PubMed/NCBI