Lipopolysaccharide-induced CCN1 production enhances interleukin-6 secretion in bronchial epithelial cells
Tóm tắt
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells. Our data illustrated that the expression levels of CCN1 and IL-6 in bronchoalveolar lavage fluid (BALF) in a lipopolysaccharide (LPS)-induced ALI mouse model were significantly elevated and the pulmonary expression of CCN1 was restricted to bronchial epithelial cells. Interestingly, both endogenous and exogenous CCN1 stimulated IL-6 production in vitro. Furthermore, LPS-induced IL-6 production in a bronchial epithelial cell line was blocked by CCN siRNA whereas CCN1 induced by LPS was sensitive to PI3K inhibition. Together, our data indicate a linear signal pathway, LPS-CCN1-IL-6, existing in bronchial epithelial cells after LPS exposure. This finding may represent an additional mechanism and a novel target for development of therapy and biomarker on ALI/ARDS.
Tài liệu tham khảo
Aman J, Weijers EM, van Nieuw Amerongen GP, Malik AB, van Hinsbergh VW. Using cultured endothelial cells to study endothelial barrier dysfunction: challenges and opportunities. Am J Physiol Lung Cell Mol Physiol. 2016;311(2):453–66.
Butt Y, Kurdowska A, Allen TC. Acute lung injury: a clinical and molecular review. Arch Pathol Lab Med. 2016;140(4):345–50.
Chen C, Fang X, Wang Y, Li Y, Wang D, Zhao X, et al. Preventive and therapeutic effects of phosphoinositide 3-kinase inhibitors on acute lung injury. Chest. 2011;140(2):391–400.
Chen C, Shi L, Li Y, Wang X, Yang S. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia. Cell Biol Toxicol. 2016;32(3):169–84.
Chen CC, Lau LF. Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol. 2009;41(4):771–83.
Choi JS, Kim KH, Lau LF. The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL-6. Mucosal Immunol. 2015;8(6):1285–96.
Fang X, Li K, Tao X, Chen C, Wang X, Wang L, et al. Effects of phosphoinositide 3-kinase on protease-induced acute and chronic lung inflammation, remodeling, and emphysema in rats. Chest. 2013;143(4):1025–35.
Grazioli S, Gil S, An D, Kajikawa O, Farnand AW, Hanson JF, et al. CYR61 (CCN1) overexpression induces lung injury in mice. American journal of physiology. Lung Cell Mol Physiol. 2015;308(8):759–65.
Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation. Cell. 2009;139(4):693–706.
Jia CE, Jiang D, Dai H, Xiao F, Wang C. Pendrin, an anion exchanger on lung epithelial cells, could be a novel target for lipopolysaccharide-induced acute lung injury mice. Am J Transl Res. 2016;8(2):981–92.
Jin Y, Kim HP, Cao J, Zhang M, Ifedigbo E, Choi AM. Caveolin-1 regulates the secretion and cytoprotection of Cyr61 in hyperoxic cell death. FASEB J. 2009;23(2):341–50.
Jin Y, Kim HP, Ifedigbo E, Lau LF, Choi AM. Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary epithelial cells. Am J Respir Cell Mol Biol. 2005;33(3):297–302.
Jun JI, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol. 2010;12(7):676–85.
Jun JI, Lau LF. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov. 2011;10(12):945–63.
Kim KH, Chen CC, Monzon RI, Lau LF. Matricellular protein CCN1 promotes regression of liver fibrosis through induction of cellular senescence in hepatic myofibroblasts. Mol Cell Biol. 2013;33(10):2078–90.
Kubota S, Takigawa M. CCN family proteins and angiogenesis: from embryo to adulthood. Angiogenesis. 2007;10(1):1–11.
Kular L, Pakradouni J, Kitabgi P, Laurent M, Martinerie C. The CCN family: a new class of inflammation modulators? Biochimie. 2011;93(3):377–88.
Kyriakides TR, Bornstein P. Matricellular proteins as modulators of wound healing and the foreign body response. Thromb Haemost. 2003;90(6):986–92.
Lai CF, Chen YM, Chiang WC, Lin SL, Kuo ML, Tsai TJ. Cysteine-rich protein 61 plays a proinflammatory role in obstructive kidney fibrosis. PLoS One. 2013;8(2):e56481.
Lai CF, Lin SL, Chiang WC, Chen YM, Wu VC, Young GH, et al. Blockade of cysteine-rich protein 61 attenuates renal inflammation and fibrosis after ischemic kidney injury. American journal of physiology. Renal Physiol. 2014;307(5):581–92.
Lau LF. CCN1/CYR61: the very model of a modern matricellular protein. Cell Molecular Life Sci CMLS. 2011;68(19):3149–63.
Lin J, Zhou Z, Huo R, Xiao L, Ouyang G, Wang L, et al. Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis. J Immunol (Baltimore, Md : 1950). 2012;188(11):5776–84.
Maron-Gutierrez T, Laffey JG, Pelosi P, Rocco PR. Cell-based therapies for the acute respiratory distress syndrome. Curr Opin Crit Care. 2014;20(1):122–31.
Moon HG, Zheng Y, An CH, Kim YK, Jin Y. CCN1 secretion induced by cigarette smoking extracts augments IL-8 release from bronchial epithelial cells. PLoS One. 2013;8(7):e68199.
Rafat N, Tonshoff B, Bierhaus A, Beck GC. Endothelial progenitor cells in regeneration after acute lung injury: do they play a role? Am J Respir Cell Mol Biol. 2013;48(4):399–405.
Raissadati A, Nykanen AI, Tuuminen R, Syrjala SO, Krebs R, Arnaudova R, et al. Systemic overexpression of matricellular protein CCN1 exacerbates obliterative bronchiolitis in mouse tracheal allografts. Trans Int. 2015;28(12):1416–25.
Sharp C, Millar AB, Medford AR. Advances in understanding of the pathogenesis of acute respiratory distress syndrome. Res Int Rev Thoracic Dis. 2015;89(5):420–34.
Slaats J, Ten Oever J, van de Veerdonk FL, Netea MG. IL-1beta/IL-6/CRP and IL-18/ferritin: distinct inflammatory programs in infections. PLoS Pathog. 2016;12(12):e1005973.
Sung SY, Liao CH, Wu HP, Hsiao WC, Wu IH, Jinpu, et al. Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer. PLoS One. 2013;8(8):e71637.
Wallace MJ, Probyn ME, Zahra VA, Crossley K, Cole TJ, Davis PG, et al. Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs. Respir Res. 2009;10:19.
Wang X, Adler KB, Erjefalt J, Bai C. Airway epithelial dysfunction in the development of acute lung injury and acute respiratory distress syndrome. Expert Rev Respirat Med. 2007;1(1):149–55.
Zhou X, Dai Q, Huang X. Neutrophils in acute lung injury. Frontiers Biosci (Landmark edition). 2012;17:2278–83.