Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice

Juan Wang; Guiming Chen; Lei Li; Sidan Luo; Bingrong Hu; Jia Xu; Haihua Luo; Shan Li; Yong Jiang

doi:10.1093/burnst/tkad006

您当前的位置：

首页 >

文章列表页 >

Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice

更新时间：2024-02-04

- Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice
- Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice
- Burns & Trauma 2023年11卷第1期
- 作者机构：
  
  Southern Medical University
- 作者简介：
- 基金信息：
  
  This study was supported by grants from the National Natural Science Foundation of China (82130063, 81971895 and 81501691), Special Support Plan for Outstanding Talents of Guangdong Province (2019JC05Y340).
- DOI：10.1093/burnst/tkad006
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-9-11，
扫描看全文
Juan Wang, Guiming Chen, Lei Li, 等. Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice[J]. Burns & Trauma, 2023,11(1).

Juan Wang, Guiming Chen, Lei Li, Sidan Luo, Bingrong Hu, Jia Xu, Haihua Luo, Shan Li, Yong Jiang, Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice, Burns & Trauma, Volume 11, 2023, tkad006, https://doi.org/10.1093/burnst/tkad006
Juan Wang, Guiming Chen, Lei Li, 等. Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice[J]. Burns & Trauma, 2023,11(1). DOI： 10.1093/burnst/tkad006.

Juan Wang, Guiming Chen, Lei Li, Sidan Luo, Bingrong Hu, Jia Xu, Haihua Luo, Shan Li, Yong Jiang, Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice, Burns & Trauma, Volume 11, 2023, tkad006, https://doi.org/10.1093/burnst/tkad006 DOI：

摘要

Abstract

BackgroundAs a damage-associated molecular pattern

the myeloid-related protein 8/14 (MRP8/14) heterodimer mediates various inflammatory diseases

such as sepsis. However

how MRP8/14 promotes lung injury by regulating the inflammatory response during endotoxemia remains largely unknown. This study aims at illuminating the pathological functions of MRP8/14 in endotoxemia.MethodsAn endotoxemic model was prepared with wild-type and myeloid cell-specific Mrp8 deletion (Mrp8ΔMC) mice for evaluating plasma cytokine levels. Lung injury was evaluated by hematoxylin and eosin (H&E) staining

injury scoring and wet-to-dry weight (W/D) ratio. The dynamic profile of interferon γ (IFNγ)-inducible protein 10 (IP-10) mRNA expression induced by macrophage MRP8/14 was determined by quantitative real-time polymerase chain reaction (qPCR). Immunoblotting was used to evaluate the increase in IP-10 level induced by activation of the JAK–STAT signaling pathway. Luciferase reporter assay was performed to detect the involvement of IRF7 in Ip-10 gene transcription. In vivo air pouch experiments were performed to determine the biological function of IP-10 induced by MRP8/14.ResultsExperiments with Mrp8ΔMC mice showed that MRP8/14 promoted the production of cytokines

including IP-10

in the bronchoalveolar lavage fluid (BALF) and lung injury in endotoxic mice. The result of qPCR showed sustained expression of Ip-10 mRNA in macrophages after treatment with MRP8/14 for 12 h. Neutralization experiments showed that the MRP8/14-induced Ip-10 expression in RAW264.7 cells was mediated by extracellular IFNβ. Western blotting with phosphorylation-specific antibodies showed that the JAK1/TYK2-STAT1 signaling pathway was activated in MRP8/14-treated RAW264.7 cells

leading to the upregulation of Ip-10 gene expression. IRF7 was further identified as a downstream regulator of the JAK–STAT pathway that mediated Ip-10 gene expression in macrophages treated with MRP8/14. In vivo air pouch experiments confirmed that the IFNβ-JAK1/TYK2-STAT1-IRF7 pathway was required for chemokine (C-X-C motif) receptor 3 (CXCR3)+ T lymphocyte migration

which promoted lung injury in the context of endotoxemia.ConclusionsIn summary

our study demonstrates that MRP8/14 induces sustained production of IP-10 via the IFNβ-JAK1/TYK2-STAT1-IRF7 pathway to attract CXCR3+ T lymphocytes into lung tissues and ultimately results in lung injury by an excessive inflammatory response in the context of endotoxemia.

关键词

Keywords

EndotoxemiaInterferon-inducible protein 10Interferon betaMacrophageMyeloid-related protein 8/14Interferon regulatory factor-7

references

1.Fein AM, Calalang-Colucci MG. Acute lung injury and acute respiratory distress syndrome in sepsis and septic shock. Crit Care Clin. 2000;16:289–317.

2.Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front Immunol. 2020;11:1722.

3.Tolle LB, Standiford TJ. Danger-associated molecular patterns (DAMPs) in acute lung injury. J Pathol. 2013;229:145–56.

4.Xiang M, Fan J. Pattern recognition receptor-dependent mechanisms of acute lung injury. Mol Med. 2010;16:69–82.

5.Foell D, Wittkowski H, Vogl T, Roth J. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol. 2007;81:28–37.

6.Leukert N, Vogl T, Strupat K, Reichelt R, Sorg C, Roth J. Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity. J Mol Biol. 2006;359:961–72.

7.Edgeworth J, Gorman M, Bennett R, Freemont P, Hogg N. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem. 1991;266:7706–13.

8.Fu X, Liu H, Huang G, Dai SS. The emerging role of neutrophils in autoimmune-associated disorders: effector, predictor, and therapeutic targets. MedComm. 2021;2:402–13.

9.Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, et al. Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med. 2007;13:1042–9.

10.Boyd JH, Kan B, Roberts H, Wang Y, Walley KR. S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products. Circ Res. 2008;102:1239–46.

11.Ehrchen JM, Sunderkotter C, Foell D, Vogl T, Roth J. The endogenous toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol. 2009;86:557–66.

12.Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J. S100A8/A9 in inflammation. Front Immunol. 2018;9:1298.

13.Sands BE. Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology. 2015;149:1275, e2–85.

14.Choi IY, Gerlag DM, Herenius MJ, Thurlings RM, Wijbrandts CA, Foell D, et al. MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis. Ann Rheum Dis. 2015;74:499–505.

15.Cai Z, Xie Q, Hu T, Yao Q, Zhao J, Wu Q, et al. S100A8/A9 in myocardial infarction: a promising biomarker and therapeutic target. Front Cell Dev Biol. 2020;8:603902.

16.Li Y, Chen B, Yang X, Zhang C, Jiao Y, Li P, et al. S100a8/a9 signaling causes mitochondrial dysfunction and cardiomyocyte death in response to ischemic/reperfusion injury. Circulation. 2019;140:751–64.

17.Wang J, Vodovotz Y, Fan L, Li Y, Liu Z, Namas R, et al. Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages. FASEB J. 2015;29:250–62.

18.Meng Q, Zhang Y, Hu LG. Targeting autophagy facilitates T lymphocyte migration by inducing the expression of CXCL10 in gastric cancer cell lines. Front Oncol. 2020;10:886.

19.Yang CW, Cho YT, Hsieh YC, Hsu SH, Chen KL, Chu CY. The interferon-gamma-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183:909–19.

20.Benigni G, Dimitrova P, Antonangeli F, Sanseviero E, Milanova V, Blom A, et al. CXCR3/CXCL10 axis regulates neutrophil-NK cell cross-talk determining the severity of experimental osteoarthritis. J Immunol. 2017;198:2115–24.

21.Herzig DS, Driver BR, Fang G, Toliver-Kinsky TE, Shute EN, Sherwood ER. Regulation of lymphocyte trafficking by CXC chemokine receptor 3 during septic shock. Am J Respir Crit Care Med. 2012;185:291–300.

22.Herzig DS, Luan L, Bohannon JK, Toliver-Kinsky TE, Guo Y, Sherwood ER. The role of CXCL10 in the pathogenesis of experimental septic shock. Crit Care. 2014;18:R113.

23.Yan Z, Luo H, Xie B, Tian T, Li S, Chen Z, et al. Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis. Nat Commun. 2021;12:308.

24.Fan J, Malik AB. Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors. Nat Med. 2003;9:315–21.

25.Gavel PK, Parmar HS, Tripathi V, Kumar N, Biswas A, Das AK. Investigations of anti-inflammatory activity of a peptide-based hydrogel using rat air pouch model. ACS Appl Mater Interfaces. 2019;11:2849–59.

26.Inada T, Sumi C, Hirota K, Shingu K, Okamoto A, Matsuo Y, et al. Mitigation of inflammation using the intravenous anesthetic dexmedetomidine in the mouse air pouch model. Immunopharmacol Immunotoxicol. 2017;39:225–32.

27.Li K, Chen G, Luo H, Li J, Liu A, Yang C, et al. MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway. J Cell Physiol. 2021;236:1375–90.

28.Davis BK. Isolation, culture, and functional evaluation of bone marrow-derived macrophages. Methods Mol Biol. 2013;1031:27–35.

29.Liu Y, Yuan Y, Li Y, Zhang J, Xiao G, Vodovotz Y, et al. Interacting neuroendocrine and innate and acquired immune pathways regulate neutrophil mobilization from bone marrow following hemorrhagic shock. J Immunol. 2009;182:572–80.

30.Liu J, Wang J, Luo H, Li Z, Zhong T, Tang J, et al. Screening cytokine/chemokine profiles in serum and organs from an endotoxic shock mouse model by LiquiChip. Sci China Life Sci. 2017;60:1242–50.

31.Gao K, Jin J, Huang C, Li J, Luo H, Li L, et al. Exosomes derived from septic mouse serum modulate immune responses via exosome-associated cytokines. Front Immunol. 2019;10:1560.

32.Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJ, de Boer JD, et al. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2016;65:575–83.

33.Ding Y, Cui Y, Hou Y, Nie H. Bone marrow mesenchymal stem cell-conditioned medium facilitates fluid resolution via miR-214-activating epithelial sodium channels. MedComm. 2020;1:376–85.

34.Di Ceglie I, van Lent P, Geven EJW, Koenders MI, Blom AB, Vogl T, et al. S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice. Arthritis Res Ther. 2021;23:216.

35.Passey RJ, Williams E, Lichanska AM, Wells C, Hu S, Geczy CL, et al. A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J Immunol. 1999;163:2209–16.

36.Dubois C, Marce D, Faivre V, Lukaszewicz AC, Junot C, Fenaille F, et al. High plasma level of S100A8/S100A9 and S100A12 at admission indicates a higher risk of death in septic shock patients. Sci Rep. 2019;9:15660.

37.Mozes T, Ben-Efraim S, Tak CJ, Heiligers JP, Saxena PR, Bonta IL. Serum levels of tumor necrosis factor determine the fatal or non-fatal course of endotoxic shock. Immunol Lett. 1991;27:157–62.

38.Clark MA, Plank LD, Connolly AB, Streat SJ, Hill AA, Gupta R, et al. Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis--a randomized, clinical trial. Crit Care Med. 1998;26:1650–9.

39.Fisher CJ, Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, et al. Treatment of septic shock with the tumor necrosis factor receptor:fc fusion protein. The soluble TNF receptor sepsis study group. N Engl J Med. 1996;334:1697–702.

40.Karin N. CXCR3 ligands in cancer and autoimmunity, chemoattraction of effector T cells, and beyond. Front Immunol. 2020;11:976.

41.Karin N, Razon H. Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine. 2018;109:24–8.

42.Hoogerwerf JJ, de Vos AF, Bresser P, van der Zee JS, Pater JM, de Boer A, et al. Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans. Am J Respir Crit Care Med. 2008;178:34–41.

43.Khan IA, MacLean JA, Lee FS, Casciotti L, DeHaan E, Schwartzman JD, et al. IP-10 is critical for effector T cell trafficking and host survival in toxoplasma gondii infection. Immunity. 2000;12:483–94.

44.Lindell DM, Lane TE, Lukacs NW. CXCL10/CXCR3-mediated responses promote immunity to respiratory syncytial virus infection by augmenting dendritic cell and CD8(+) T cell efficacy. Eur J Immunol. 2008;38:2168–79.

45.Umeda K, Goto Y, Watanabe K, Ushio N, Fereig RM, Ihara F, et al. Transcriptomic analysis of the effects of chemokine receptor CXCR3 deficiency on immune responses in the mouse brain during toxoplasma gondii infection. Microorganisms. 2021;9.

46.Harvey CE, Post JJ, Palladinetti P, Freeman AJ, Ffrench RA, Kumar RK, et al. Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. J Leukoc Biol. 2003;74:360–9.

47.Ichikawa A, Kuba K, Morita M, Chida S, Tezuka H, Hara H, et al. CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. Am J Respir Crit Care Med. 2013;187:65–77.

48.Ferrari SM, Fallahi P, Ruffilli I, Elia G, Ragusa F, Paparo SR, et al. Immunomodulation of CXCL10 secretion by hepatitis C virus: could CXCL10 be a prognostic marker of chronic hepatitis C? J Immunol Res. 2019;2019:5878960.

49.Groom JR, Luster AD. CXCR3 in T cell function. Exp Cell Res. 2011;317:620–31.

50.Ali A, Canaday LM, Feldman HA, Cevik H, Moran MT, Rajaram S, et al. Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues. J Clin Invest. 2021;131:e146686.

51.Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med. 2005;171:850–7.

52.Li CX, Ling CC, Shao Y, Xu A, Li XC, Ng KT, et al. CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation. J Hepatol. 2016;65:944–52.

53.Karaghiosoff M, Steinborn R, Kovarik P, Kriegshauser G, Baccarini M, Donabauer B, et al. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003;4:471–7.

54.Rackov G, Shokri R, De Mon MA, Martinez AC, Balomenos D. The role of IFN-beta during the course of sepsis progression and its therapeutic potential. Front Immunol. 2017;8:493.

55.Kitai R, Zhao ML, Zhang N, Hua LL, Lee SC. Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta. J Neuroimmunol. 2000;110:230–9.

56.Mariani MK, Dasmeh P, Fortin A, Caron E, Kalamujic M, Harrison AN, et al. The combination of IFN beta and TNF induces an antiviral and immunoregulatory program via non-canonical pathways involving STAT2 and IRF9. Cell. 2019;8:919.

57.Ohmori Y, Hamilton TA. Requirement for STAT1 in LPS-induced gene expression in macrophages. J Leukoc Biol. 2001;69:598–604.

58.Ren Y, Zhao Y, Lin D, Xu X, Zhu Q, Yao J, et al. The type I interferon-IRF7 axis mediates transcriptional expression of Usp25 gene. J Biol Chem. 2016;291:13206–15.

59.Honda K, Taniguchi T. IRFs: master regulators of signalling by toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006;6:644–58.

60.Majumder S, Zhou LZ, Chaturvedi P, Babcock G, Aras S, Ransohoff RM. p48/STAT-1alpha-containing complexes play a predominant role in induction of IFN-gamma-inducible protein, 10 kDa (IP-10) by IFN-gamma alone or in synergy with TNF-alpha. J Immunol. 1998;161:4736–44.

61.Ohmori Y, Hamilton TA. The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha. J Immunol. 1995;154:5235–44.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids

Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease