Soluble receptor for advanced glycation end-products enhanced the production of IFN-γ through the NF-κB pathway in macrophages recruited by ischemia/reperfusion

Zhang,Xiuling; Cao,Xianxian; Dang,Mengqiu; Wang,Hongxia; Chen,Buxing; Du,Fenghe; Li,Huihua; Zeng,Xiangjun; Guo,Caixia

doi:10.3892/ijmm.2019.4152

Soluble receptor for advanced glycation end-products enhanced the production of IFN-γ through the NF-κB pathway in macrophages recruited by ischemia/reperfusion

Authors:
- Xiuling Zhang
- Xianxian Cao
- Mengqiu Dang
- Hongxia Wang
- Buxing Chen
- Fenghe Du
- Huihua Li
- Xiangjun Zeng
- Caixia Guo
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Affiliations: Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100070, P.R. China, Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China, Department of Cardiology, Institute of Cardiovascular Disease, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
Published online on: March 29, 2019 https://doi.org/10.3892/ijmm.2019.4152
Pages: 2507-2515

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Abstract

The current study investigated the role of sRAGE in the production of IFN‑γ in macrophages with I/R treatment. The number of macrophages in myocardial tissues treated with I/R with or without sRAGE was determined via immunohistochemical staining. Proliferative activity of macrophages was analyzed by a 5‑BrdU incorporation assay. Differentiation of macrophages was detected via immunofluorescence staining of iNOS (M1 macrophage marker). IFN‑γ production, due to sRAGE stimulation, in Raw 264.7 macrophages and the NF‑κB signaling pathway were measured using western blotting. A ChIP assay was used to examine the interactions between NF‑κB and the promoter of IFN‑γ. The results showed that the number of macrophages in I/R‑treated myocardial tissues was increased following sRAGE infusion. Proliferation of macrophages was increased significantly in the presence of sRAGE; after I/R treatment, the cells preferred to differentiate into M1 macrophages. IFN‑γ expression in Raw 264.7 macrophages was suppressed by an NF‑κB inhibitor (Bay117082) but enhanced by sRAGE, with or without I/R treatment. Furthermore, sRAGE increased the phosphorylation of IκB, IKK and NF‑κB, as well as the translocation of NF‑κB into the nucleus of Raw 264.7 macrophages, with or without I/R treatment. ChIP results showed that sRAGE promoted NF‑κB binding to the promoter of IFN‑γ in Raw 264.7 macrophages. Therefore, the findings of the present study indicated that sRAGE protected the heart from I/R injuries, which might be mediated by promoting infiltration and the differentiation of macrophages into M1, which would then synthesize and secrete IFN‑γ through activating the NF‑κB signaling pathway.

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1	Maneechote C, Palee S, Chattipakorn SC and Chattipakorn N: Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury. J Cell Mol Med. 21:2643–2653. 2017. View Article : Google Scholar : PubMed/NCBI
2	Kocman EA, Ozatik O, Sahin A, Guney T, Kose AA, Dag I, Alatas O and Cetin C: Effects of ischemic preconditioning protocols on skeletal muscle ischemia-reperfusion injury. J Surg Res. 193:942–952. 2015. View Article : Google Scholar
3	Kunecki M, Plazak W, Podolec P and Golba KS: Effects of endogenous cardioprotective mechanisms on ischemia-reperfusion injury. Postepy Hig Med Dosw (Online). 71:20–31. 2017. View Article : Google Scholar
4	Hauerslev M, Mork SR, Pryds K, Contractor H, Hansen J, Jespersen NR, Johnsen J, Heusch G, Kleinbongard P, Kharbanda R, et al: Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning. Am J Physiol Heart Circ Physiol. 315:H150–H158. 2018. View Article : Google Scholar : PubMed/NCBI
5	Wang C, Li H, Wang S, Mao X, Yan D, Wong SS, Xia Z and Irwin MG: Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PKC-/STAT3 signaling in diabetic rats. Cell Physiol Biochem. 45:2107–2121. 2018. View Article : Google Scholar
6	Yuan Y, Cao W, Hong Y, Guo X, Wang Y, Wang Y, Wang X and Xu P: Tilianin pretreatment prevents myocardial ischemia-reperfusion injury via preservation of mitochondrial function in rat heart. Phytomedicine. 34:106–114. 2017. View Article : Google Scholar : PubMed/NCBI
7	Yang Y, Zhao L and Ma J: Penehyclidine hydrochloride preconditioning provides cardiac protection in a rat model of myocardial ischemia/reperfusion injury via the mechanism of mitochondrial dynamics mechanism. Eur J Pharmacol. 813:130–139. 2017. View Article : Google Scholar : PubMed/NCBI
8	Cai XY, Lu L, Wang YN, Jin C, Zhang RY, Zhang Q, Chen QJ and Shen WF: Association of increased S100B, S100A6 and S100P in serum levels with acute coronary syndrome and also with the severity of myocardial infarction in cardiac tissue of rat models with ischemia-reperfusion injury. Atherosclerosis. 217:536–542. 2011. View Article : Google Scholar : PubMed/NCBI
9	Wautier JL, Zoukourian C, Chappey O, Wautier MP, Guillausseau PJ, Cao R, Hori O, Stern D and Schmidt AM: Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy, Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest. 97:238–243. 1996. View Article : Google Scholar : PubMed/NCBI
10	Dattilo BM, Fritz G, Leclerc E, Kooi CW, Heizmann CW and Chazin WJ: The extracellular region of the receptor for advanced glycation end products is composed of two independent structural units. Biochemistry. 46:6957–6970. 2007. View Article : Google Scholar : PubMed/NCBI
11	Raucci A, Cugusi S, Antonelli A, Barabino SM, Monti L, Bierhaus A, Reiss K, Saftig P and Bianchi ME: A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB. 22:3716–3727. 2008. View Article : Google Scholar
12	Yonchuk JG, Silverman EK, Bowler RP, Agusti A, Lomas DA, Miller BE, Tal-Singer R and Mayer RJ: Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. Am J Respir Crit Care Med. 192:785–792. 2015. View Article : Google Scholar : PubMed/NCBI
13	Pullerits R, Brisslert M, Jonsson IM and Tarkowski A: Soluble receptor for advanced glycation end products triggers a proinflammatory cytokine cascade via beta2 integrin Mac-1. Arthritis Rheum. 54:3898–3907. 2006. View Article : Google Scholar : PubMed/NCBI
14	Yan SF, Yan SD, Herold K, Ramsamy R and Schmidt AM: Receptor for advanced glycation end products and the cardiovascular complications of diabetes and beyond: Lessons from AGEing. Endocrinol Metab Clin North Am. 35:511–524. 2006. View Article : Google Scholar : PubMed/NCBI
15	Schmidt AM, Yan SD, Yan SF and Stern DM: The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 108:949–955. 2001. View Article : Google Scholar : PubMed/NCBI
16	Dang M, Zeng X, Chen B, Wang H, Li H, Du F and Guo C: Interferon-gamma mediates the protective effects of soluble receptor for advanced glycation end-product in myocardial isch-emia/reperfusion. Lab Invest. 99:358–370. 2019. View Article : Google Scholar
17	Darwich L, Coma G, Pena R, Bellido R, Blanco EJ, Este JA, Borras FE, Clotet B, Ruiz L, Rosell A, et al: Secretion of interferon-gamma by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18. Immunology. 126:386–393. 2009. View Article : Google Scholar :
18	Deng Y, Chu J, Ren Y, Fan Z, Ji X, Mundy-Bosse B, Yuan S, Hughes T, Zhang J, Cheema B, et al: The natural product phyllanthusmin C enhances IFN-gamma production by human NK cells through upregulation of TLR-mediated NF-kappaB signaling. J Immunol. 193:2994–3002. 2014. View Article : Google Scholar : PubMed/NCBI
19	Kim BR, Chun S and Cho D: Association of neutrophil-to-lymphocyte ratio and natural killer cell activity revealed by measurement of interferon-gamma levels in a healthy population. J Clin Lab Anal. 33:e226402018. View Article : Google Scholar : PubMed/NCBI
20	Kang HB, Ahn KS, Oh SR and Kim JW: Genkwadaphnin induces IFN-gamma via PKD1/NF-kappaB/STAT1 dependent pathway in NK-92 cells. PLoS One. 9:e1151462014. View Article : Google Scholar
21	Pan Z, Sun X, Ren J, Li X, Gao X, Lu C, Zhang Y, Sun H, Wang Y, Wang H, et al: miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS One. 7:e505152012. View Article : Google Scholar : PubMed/NCBI
22	Zhang BH, Wang W, Wang H, Yin J and Zeng XJ: Promoting effects of the adipokine, apelin, on diabetic nephropathy. PLoS One. 8:e604572013. View Article : Google Scholar : PubMed/NCBI
23	Brisslert M, Amu S and Pullerits R: Intra-peritoneal sRAGE treatment induces alterations in cellular distribution of CD19(+), CD3 (+) and Mac-1 (+) cells in lymphoid organs and peritoneal cavity. Cell Tissue Res. 351:139–148. 2013. View Article : Google Scholar
24	Wang Y, Wang H, Piper MG, McMaken S, Mo X, Opalek J, Schmidt AM and Marsh CB: sRAGE induces human monocyte survival and differentiation. J Immunol. 185:1822–1835. 2010. View Article : Google Scholar : PubMed/NCBI
25	Ganz T: Macrophage function. New Horiz. 1:23–27. 1993.PubMed/NCBI
26	Ko GJ, Boo CS, Jo SK, Cho WY and Kim HK: Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury. Nephrol Dial Transplant. 23:842–852. 2008. View Article : Google Scholar
27	Zhang L and Wang CC: Inflammatory response of macrophages in infection. Hepatobiliary & pancreatic diseases international. Hepatobiliary Pancreat Dis Int. 13:138–152. 2014. View Article : Google Scholar : PubMed/NCBI
28	Zhou D, Huang C, Lin Z, Zhan S, Kong L, Fang C and Li J: Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal. 26:192–197. 2014. View Article : Google Scholar
29	Khan MA, Assiri AM and Broering DC: Complement and macrophage crosstalk during process of angiogenesis in tumor progression. J Biomed Sci. 22:58–67. 2015. View Article : Google Scholar : PubMed/NCBI
30	Saqib U, Sarkar S, Suk K, Mohammad O, Baig MS and Savai R: Phytochemicals as modulators of M1-M2 macrophages in inflammation. Oncotarget. 9:17937–17950. 2018. View Article : Google Scholar : PubMed/NCBI
31	Guo CX, Jiang X, Zeng XJ, Wang HX, Li HH, Du FH and Chen BX: Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system. Free Radic Biol Med. 94:17–26. 2016. View Article : Google Scholar : PubMed/NCBI
32	Wang Z, Zhou Y, Yu Y, He K and Cheng LM: Lipopolysaccharide preconditioning increased the level of regulatory B cells in the spleen after acute ischaemia/reperfusion in mice. Brain Res. 1701:46–57. 2018. View Article : Google Scholar : PubMed/NCBI
33	Xu C, Zhu H, Shen R, Feng Q, Zhou H and Zhao Z: IL-35 is a protective immunomodulator in brain ischemic injury in mice. Neurochem Res. 43:1454–1463. 2018. View Article : Google Scholar : PubMed/NCBI