Pentraxin 3 promotes airway inflammation in experimental asthma
Tóm tắt
Pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation. Recently, it has been reported that PTX3 deficiency enhances interleukin (IL)-17A–dominant pulmonary inflammation in an ovalbumin (OVA)-induced mouse asthma model. However, whether PTX3 treatment would provide protection against allergic airway inflammation has not been clearly elucidated. The goal of this study was to further investigate the effect of recombinant PTX3 administration on the phenotype of asthma.
C57BL/6 J mice were sensitized and challenged with OVA to induce eosinophilic asthma model, as well as sensitized with OVA plus LPS and challenged with OVA to induce neutrophilic asthma model. We evaluated effect of recombinant PTX3 on asthma phenotype through both asthma models. The bronchoalveolar lavage fluid (BALF) inflammatory cells and cytokines, airway hyperresponsiveness, and pathological alterations of the lung tissues were assessed.
In both eosinophilic and neutrophilic asthma models, PTX3 treatment provoked airway hyperresponsiveness, concomitant with increased inflammatory cytokines IL-4, IL-17, eotaxin, and transforming growth factor (TGF)-β1 and aggravated airway accumulation of inflammatory cells, especially eosinophils and neutrophils. In histological analysis of the lung tissue, administration of PTX3 promoted inflammatory cells infiltration, mucus production, and collagen deposition. In addition, PTX3 also significantly enhanced STAT3 phosphorylation in lung tissue.
Our results show that exogenous PTX3 can exacerbate multiple asthmatic features by promoting both eosinophils and neutrophils lung infiltration and provide new evidence to better understand the complex role of PTX3 in allergic airway inflammation.
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Tài liệu tham khảo
Carr TF, Zeki AA, Kraft M. Eosinophilic and Noneosinophilic Asthma. Am J Respir Crit Care Med. 2018;197:22–37.
McGrath KW, Icitovic N, Boushey HA, Lazarus SC, Sutherland ER, Chinchilli VM, Fahy JV. Asthma Clinical Research Network of the National Heart L, Blood I: A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med. 2012;185:612–9.
Garlanda C, Bottazzi B, Magrini E, Inforzato A, Mantovani A. PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer. Physiol Rev. 2018;98:623–39.
Bottazzi B, Inforzato A, Messa M, Barbagallo M, Magrini E, Garlanda C, Mantovani A. The pentraxins PTX3 and SAP in innate immunity, regulation of inflammation and tissue remodelling. J Hepatol. 2016;64:1416–27.
Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature. 2002;420:182–6.
Moalli F, Paroni M, Veliz Rodriguez T, Riva F, Polentarutti N, Bottazzi B, Valentino S, Mantero S, Nebuloni M, Mantovani A, et al. The therapeutic potential of the humoral pattern recognition molecule PTX3 in chronic lung infection caused by Pseudomonas aeruginosa. J Immunol. 2011;186:5425–34.
Perea L, Coll M, Sanjurjo L, Blaya D, Taghdouini AE, Rodrigo-Torres D, Altamirano J, Graupera I, Aguilar-Bravo B, Llopis M, et al. Pentraxin-3 modulates lipopolysaccharide-induced inflammatory response and attenuates liver injury. Hepatology. 2017;66:953–68.
Han B, Haitsma JJ, Zhang Y, Bai X, Rubacha M, Keshavjee S, Zhang H, Liu M. Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury. Intensive Care Med. 2011;37:334–42.
Lech M, Rommele C, Grobmayr R, Eka Susanti H, Kulkarni OP, Wang S, Grone HJ, Uhl B, Reichel C, Krombach F, et al. Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury. Kidney Int. 2013;83:647–61.
Souza DG, Soares AC, Pinho V, Torloni H, Reis LF, Teixeira MM, Dias AA. Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. Am J Pathol. 2002;160:1755–65.
Foo SS, Chen W, Taylor A, Sheng KC, Yu X, Teng TS, Reading PC, Blanchard H, Garlanda C, Mantovani A, et al. Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation. PLoS Pathog. 2015;11:e1004649.
Carrizzo A, Lenzi P, Procaccini C, Damato A, Biagioni F, Ambrosio M, Amodio G, Remondelli P, Del Giudice C, Izzo R, et al. Pentraxin 3 Induces Vascular Endothelial Dysfunction Through a P-selectin/Matrix Metalloproteinase-1 Pathway. Circulation. 2015;131:1495–505 discussion 1505.
Zhang J, Shan L, Koussih L, Redhu NS, Halayko AJ, Chakir J, Gounni AS. Pentraxin 3 (PTX3) expression in allergic asthmatic airways: role in airway smooth muscle migration and chemokine production. PLoS One. 2012;7:e34965.
Kim MJ, Lee HS, Sol IS, Kim MN, Hong JY, Lee KE, Kim YH, Kim KW, Sohn MH, Kim KE. Sputum pentraxin 3 as a candidate to assess airway inflammation and remodeling in childhood asthma. Medicine (Baltimore). 2016;95:e5677.
Gao P, Zhao J, Xie J. PTX3 and D-dimer in children with asthma: A real-world study-Reply. Clin Exp Allergy. 2019;49:552.
Balhara J, Shan L, Zhang J, Muhuri A, Halayko AJ, Almiski MS, Doeing D, McConville J, Matzuk MM, Gounni AS. Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival. J Allergy Clin Immunol. 2017;139:950–963 e959.
Gao P, Tang K, Wang M, Yang Q, Xu Y, Wang J, Zhao J, Xie J. Pentraxin levels in non-eosinophilic versus eosinophilic asthma. Clin Exp Allergy. 2018;48:981–9.
Kim SR, Kim DI, Kang MR, Lee KS, Park SY, Jeong JS, Lee YC. Endoplasmic reticulum stress influences bronchial asthma pathogenesis by modulating nuclear factor kappaB activation. J Allergy Clin Immunol. 2013;132:1397–408.
Rivieccio V, Esposito A, Bellofiore P, Palladino P, Sassano M, Colombo M, Verdoliva A. High-level expression and efficient purification of recombinant human long pentraxin PTX3 in Chinese hamster ovary cells. Protein Expr Purif. 2007;51:49–58.
Myou S, Leff AR, Myo S, Boetticher E, Tong J, Meliton AY, Liu J, Munoz NM, Zhu X. Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. J Exp Med. 2003;198:1573–82.
Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway epithelial STAT3 is required for allergic inflammation in a murine model of asthma. J Immunol. 2007;178:6191–9.
Sun H, Tian J, Xian W, Xie T, Yang X. Pentraxin-3 Attenuates renal damage in diabetic nephropathy by promoting M2 macrophage differentiation. Inflammation. 2015;38:1739–47.
Shiraki A, Kotooka N, Komoda H, Hirase T, Oyama JI, Node K. Pentraxin-3 regulates the inflammatory activity of macrophages. Biochem Biophys Rep. 2016;5:290–5.
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, Olivenstein R, Elias J, Chakir J. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001;108:430–8.
Barczyk A, Pierzchala W, Sozanska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 2003;97:726–33.
Sun YC, Zhou QT, Yao WZ. Sputum interleukin-17 is increased and associated with airway neutrophilia in patients with severe asthma. Chin Med J. 2005;118:953–6.
Bullens DM, Truyen E, Coteur L, Dilissen E, Hellings PW, Dupont LJ, Ceuppens JL. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res. 2006;7:135.
Doe C, Bafadhel M, Siddiqui S, Desai D, Mistry V, Rugman P, McCormick M, Woods J, May R, Sleeman MA, et al. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest. 2010;138:1140–7.
Hoshino H, Laan M, Sjostrand M, Lotvall J, Skoogh BE, Linden A. Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo. J Allergy Clin Immunol. 2000;105:143–9.
Fujisawa T, Chang MM, Velichko S, Thai P, Hung LY, Huang F, Phuong N, Chen Y, Wu R. NF-kappaB mediates IL-1beta- and IL-17A-induced MUC5B expression in airway epithelial cells. Am J Respir Cell Mol Biol. 2011;45:246–52.
Chang Y, Al-Alwan L, Risse PA, Halayko AJ, Martin JG, Baglole CJ, Eidelman DH, Hamid Q. Th17-associated cytokines promote human airway smooth muscle cell proliferation. FASEB J. 2012;26:5152–60.
Chang Y, Al-Alwan L, Risse PA, Roussel L, Rousseau S, Halayko AJ, Martin JG, Hamid Q, Eidelman DH. TH17 cytokines induce human airway smooth muscle cell migration. J Allergy Clin Immunol. 2011;127:1046–1053 e1041–1042.
Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, et al. IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012;18:547–54.
Smith E, Stark MA, Zarbock A, Burcin TL, Bruce AC, Vaswani D, Foley P, Ley K. IL-17A inhibits the expansion of IL-17A-producing T cells in mice through “short-loop” inhibition via IL-17 receptor. J Immunol. 2008;181:1357–64.
Silverpil E, Wright AK, Hansson M, Jirholt P, Henningsson L, Smith ME, Gordon SB, Iwakura Y, Gjertsson I, Glader P, Linden A. Negative feedback on IL-23 exerted by IL-17A during pulmonary inflammation. Innate Immun. 2013;19:479–92.
Magrini E, Mantovani A, Garlanda C. The Dual Complexity of PTX3 in Health and Disease: A Balancing Act? Trends Mol Med. 2016;22:497–510.
Souza DG, Amaral FA, Fagundes CT, Coelho FM, Arantes RM, Sousa LP, Matzuk MM, Garlanda C, Mantovani A, Dias AA, Teixeira MM. The long pentraxin PTX3 is crucial for tissue inflammation after intestinal ischemia and reperfusion in mice. Am J Pathol. 2009;174:1309–18.