{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:10:10Z","timestamp":1771240210481,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["HL151397"],"award-info":[{"award-number":["HL151397"]}]},{"name":"National Institute of Health","award":["ES025815"],"award-info":[{"award-number":["ES025815"]}]},{"name":"National Institute of Health","award":["CA282561"],"award-info":[{"award-number":["CA282561"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alveolar inflammation, elevated interleukin-17A (IL-17A), and fibrin deposition are common features in all forms of lung injury followed by fibrotic repair. Type II alveolar epithelial cell (AEC) viability, regulated by tumor suppressor protein p53 and changes in uPA-mediated fibrinolysis, has been linked to lung injury and pulmonary fibrosis (PF). Nevertheless, mechanistic details linking increased IL-17A with p53 and PAI-1 to lung injury and remodeling remain unclear. We found that IL-17A and its receptor (IL-17RA) are induced during various lung injuries. IL-17A augments IL-17RA, p53 and downstream PAI-1 with a concurrent decrease in uPA and its receptor (uPAR) in AECs. These changes promote AEC apoptosis, alveolar injury and PF. In addition, IL-17A causes a dose-dependent increase in IL-17RA and profibrogenic markers in lung fibroblasts (LFs), suggesting myofibroblast differentiation. We further found that inhibition of IL-17A by caveolin-1 scaffolding domain peptide (CSP) or its 7-mer deletion fragment (CSP7) inhibits AEC apoptosis, lung inflammation, and profibrogenic markers in LFs and PF. Further, treatment of mice with bleomycin-induced lung injury using CSP7, an anti-IL-17A antibody, or an IL-17RA blocking antibody attenuates total lung hydroxyproline and soluble collagen content, as well as levels of profibrogenic markers. These observations support the role of IL-17A\/IL-17RA signaling in lung injury and post-injury remodeling.<\/jats:p>","DOI":"10.3390\/ijms27041841","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-17A Orchestrates Lung Injury and Remodeling Through p53 and uPA System Crosstalk"],"prefix":"10.3390","volume":"27","author":[{"given":"Durgesh Nandini","family":"Das","sequence":"first","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-6396","authenticated-orcid":false,"given":"Akarsha","family":"Balnadupete","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1298-9498","authenticated-orcid":false,"given":"Rashmi","family":"Shetty","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkadesa Perumal","family":"Gopu","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rushil","family":"Sajjan","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yashodhar P.","family":"Bhandary","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-5743","authenticated-orcid":false,"given":"Amarnath S.","family":"Marudamuthu","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Oliver","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aarav","family":"Patel","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aryan","family":"Patel","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buka","family":"Samten","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Tang","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah E.","family":"Citrin","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5230-1062","authenticated-orcid":false,"given":"Jay","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, 4502 Medical Dr., San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreerama","family":"Shetty","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19570","DOI":"10.1074\/jbc.M710268200","article-title":"Regulation of plasminogen activator inhibitor-1 expression by tumor suppressor protein p53","volume":"283","author":"Shetty","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.ajpath.2016.12.020","article-title":"p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis","volume":"187","author":"Shetty","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1165\/rcmb.2011-0390OC","article-title":"Regulation of airway and alveolar epithelial cell apoptosis by p53-Induced plasminogen activator inhibitor-1 during cigarette smoke exposure injury","volume":"47","author":"Shetty","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajpath.2013.03.022","article-title":"Regulation of lung injury and fibrosis by p53-mediated changes in urokinase and plasminogen activator inhibitor-1","volume":"183","author":"Bhandary","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"L783","DOI":"10.1152\/ajplung.00291.2016","article-title":"Regulation of p53-mediated changes in the uPA-fibrinolytic system and in lung injury by loss of surfactant protein C expression in alveolar epithelial cells","volume":"312","author":"Puthusseri","year":"2017","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"L463","DOI":"10.1152\/ajplung.00099.2011","article-title":"Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system","volume":"302","author":"Bhandary","year":"2012","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"L689","DOI":"10.1152\/ajplung.00178.2022","article-title":"Caveolin-1-derived peptide attenuates cigarette smoke-induced airway and alveolar epithelial injury","volume":"325","author":"Das","year":"2023","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rana, T., Jiang, C., Banerjee, S., Yi, N., Zmijewski, J.W., Liu, G., and Liu, R.M. (2023). PAI-1 Regulation of p53 Expression and Senescence in Type II Alveolar Epithelial Cells. Cells, 12.","DOI":"10.3390\/cells12152008"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/ncb1448","article-title":"Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence","volume":"8","author":"Kortlever","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.taap.2015.01.007","article-title":"Role of p53-fibrinolytic system cross-talk in the regulation of quartz-induced lung injury","volume":"283","author":"Bhandary","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.18632\/aging.203890","article-title":"Senescence-associated tumor growth is promoted by 12-Lipoxygenase","volume":"14","author":"Patil","year":"2022","journal-title":"Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104022","DOI":"10.1016\/j.isci.2022.104022","article-title":"Caveolin-1 peptide regulates p53-microRNA-34a feedback in fibrotic lung fibroblasts","volume":"25","author":"Hogan","year":"2022","journal-title":"iScience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eaat2848","DOI":"10.1126\/scitranslmed.aat2848","article-title":"Caveolin-1-derived peptide limits development of pulmonary fibrosis","volume":"11","author":"Marudamuthu","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"L480","DOI":"10.1152\/ajplung.00295.2024","article-title":"p53-miR-34a feedback in lung fibroblasts regulates antifibrotic effects of CSP7, nintedanib, and pirfenidone","volume":"329","author":"Fan","year":"2025","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1165\/rcmb.2023-0453OC","article-title":"CSP7 Protects Alveolar Epithelial Cells by Targeting p53-Fibrinolytic Pathways During Lung Injuries","volume":"72","author":"Puthusseri","year":"2024","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11086","DOI":"10.1038\/s41598-022-14832-4","article-title":"Caveolin-1 scaffolding domain peptide abrogates autophagy dysregulation in pulmonary fibrosis","volume":"12","author":"Venkatesan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23961","DOI":"10.18632\/oncotarget.8208","article-title":"Plasminogen activator inhibitor-1 enhances radioresistance and aggressiveness of non-small cell lung cancer cells","volume":"7","author":"Kang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/cdd.2017.169","article-title":"How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?","volume":"25","author":"Aubrey","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"691","DOI":"10.2353\/ajpath.2008.070930","article-title":"Essential role of plasminogen activator inhibitor type-1 in radiation enteropathy","volume":"172","author":"Milliat","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s13238-011-1006-5","article-title":"Structure and function of interleukin-17 family cytokines","volume":"2","author":"Zhang","year":"2011","journal-title":"Protein Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/intimm\/dxab075","article-title":"Interleukin-17 family members in health and disease","volume":"33","author":"Chung","year":"2021","journal-title":"Int. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.cyto.2013.07.022","article-title":"IL-17 family: Cytokines, receptors and signaling","volume":"64","author":"Gu","year":"2013","journal-title":"Cytokine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1136\/ard-2023-224479","article-title":"New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: Identification of the bioactive sequence (nIL-17) for IL-17A\/F function","volume":"82","author":"Saviano","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-023-01620-3","article-title":"The IL-17 family in diseases: From bench to bedside","volume":"8","author":"Huangfu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/prd.12083","article-title":"Basic biology and role of interleukin-17 in immunity and inflammation","volume":"69","author":"Zenobia","year":"2000","journal-title":"Periodontology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2567.2011.03465.x","article-title":"The interleukin-17 cytokine family: Critical players in host defence and inflammatory diseases","volume":"134","author":"Pappu","year":"2011","journal-title":"Immunology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The IL-17 Family of Cytokines in Health and Disease","volume":"50","author":"McGeachy","year":"2019","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.immuni.2011.02.012","article-title":"Functional specialization of interleukin-17 family members","volume":"34","author":"Iwakura","year":"2011","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1038\/emi.2013.58","article-title":"IL-17 cytokines in immunity and inflammation","volume":"2","author":"Jin","year":"2013","journal-title":"Emerg. Microbes Infect."},{"key":"ref_30","first-page":"21","article-title":"Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis","volume":"9","author":"Nie","year":"2022","journal-title":"Mil. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cytogfr.2025.01.002","article-title":"Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders","volume":"83","author":"Saran","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1365-2567.2008.03017.x","article-title":"Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens","volume":"126","author":"Curtis","year":"2009","journal-title":"Immunology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.immuni.2013.12.002","article-title":"IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells","volume":"40","author":"Bar","year":"2014","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a028522","DOI":"10.1101\/cshperspect.a028522","article-title":"Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications","volume":"10","author":"Monin","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1084\/jem.20070406","article-title":"IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells","volume":"204","author":"Wang","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nri2586","article-title":"Structure and signalling in the IL-17 receptor family","volume":"9","author":"Gaffen","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102970","DOI":"10.1016\/j.redox.2023.102970","article-title":"Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation","volume":"68","author":"Song","year":"2023","journal-title":"Redox Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41584-023-01004-5","article-title":"IL-17A and IL-17F in tissue homeostasis, inflammation and regeneration","volume":"19","author":"Adamopoulos","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1465-9921-12-43","article-title":"CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease","volume":"12","author":"Chang","year":"2011","journal-title":"Respir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12931-017-0534-9","article-title":"Increased IL-17RA and IL-17RC in End-Stage COPD and the Contribution to Mast Cell Secretion of FGF-2 and VEGF","volume":"18","author":"Roos","year":"2017","journal-title":"Respir. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.resinv.2023.05.005","article-title":"Pulmonary fibrosis and type-17 immunity","volume":"61","author":"Senoo","year":"2023","journal-title":"Respir. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"L122","DOI":"10.1152\/ajplung.00301.2016","article-title":"Role of IL-17A in murine models of COPD airway disease","volume":"312","author":"Yanagisawa","year":"2017","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, K., Pociask, D.A., McAleer, J.P., Chan, Y.R., Alcorn, J.F., Kreindler, J.L., Keyser, M.R., Shapiro, S.D., Houghton, A.M., and Kolls, J.K. (2011). IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020333"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1465-9921-14-5","article-title":"IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice","volume":"14","author":"Kurimoto","year":"2013","journal-title":"Respir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.4049\/jimmunol.1004081","article-title":"Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGF-beta1-dependent and -independent mechanisms","volume":"187","author":"Mi","year":"2011","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119864","DOI":"10.1016\/j.bbamcr.2024.119864","article-title":"IL-17A\u2019s role in exacerbating radiation-induced lung injury: Autophagy impairment via the PP2A-mTOR pathway","volume":"1872","author":"Liu","year":"2025","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.taap.2013.11.012","article-title":"Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL\/6 mice","volume":"275","author":"Chen","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2567.2009.03240.x","article-title":"Interleukin-17 and its target genes: Mechanisms of interleukin-17 function in disease","volume":"129","author":"Onishi","year":"2010","journal-title":"Immunology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1111\/jcmm.17600","article-title":"IL-17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells","volume":"26","author":"Xiao","year":"2022","journal-title":"J. Cell Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5730395","DOI":"10.1155\/2018\/5730395","article-title":"Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease","volume":"2018","author":"Boukhenouna","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00011-022-01594-y","article-title":"Particulate matter in COPD pathogenesis: An overview","volume":"71","author":"Kaur","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2147\/COPD.S5098","article-title":"Particulate matter air pollution exposure: Role in the development and exacerbation of chronic obstructive pulmonary disease","volume":"4","author":"Ling","year":"2009","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113787","DOI":"10.1016\/j.fct.2023.113787","article-title":"Evaluation of cigarette smoke-induced oxidative stress and inflammation in BEAS-2B cells based on a lung microfluidic chip","volume":"176","author":"Xue","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bezerra, F.S., Lanzetti, M., Nesi, R.T., Nagato, A.C., Silva, C.P.E., Kennedy-Feitosa, E., Melo, A.C., Cattani-Cavalieri, I., Porto, L.C., and Valenca, S.S. (2023). Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries. Antioxidants, 12.","DOI":"10.3390\/antiox12030548"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"117313","DOI":"10.1016\/j.envpol.2021.117313","article-title":"Airborne particulate matter induces oxidative damage, DNA adduct formation and alterations in DNA repair pathways","volume":"287","author":"Chirino","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sun, X., Zhang, X., He, Y., Du, X., Cai, Q., and Liu, Z. (2025). CD4(+)T and CD8(+)T cells profile in lung inflammation and fibrosis: Targets and potential therapeutic drugs. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1562892"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Al Heialy, S., Gaudet, M., Ramakrishnan, R.K., Mogas, A., Salameh, L., Mahboub, B., and Hamid, Q. (2020). Contribution of IL-17 in Steroid Hyporesponsiveness in Obese Asthmatics Through Dysregulation of Glucocorticoid Receptors alpha and beta. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01724"},{"key":"ref_58","first-page":"482","article-title":"Interleukin-17A Promotes Airway Remodeling in Chronic Obstructive Pulmonary Disease by Activating C-X-C Motif Chemokine Ligand 12 Secreted by Lung Fibroblasts","volume":"11","author":"Chen","year":"2024","journal-title":"Chronic Obs. Pulm. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1365-2249.2009.03965.x","article-title":"T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients","volume":"157","author":"Caramori","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/toxsci\/kfac089","article-title":"Caveolin-1 and its functional peptide CSP7 affect silica-induced pulmonary fibrosis by regulating fibroblast glutaminolysis","volume":"190","author":"Li","year":"2022","journal-title":"Toxicol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1667\/RR1522.1","article-title":"Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice","volume":"173","author":"Lee","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2451323","DOI":"10.1002\/eji.202451323","article-title":"Innate T-cell-derived IL-17A\/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-beta1-induced lung fibrosis in mice","volume":"54","author":"Moog","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1165\/ajrcmb.14.4.8600933","article-title":"Isolation and primary culture of murine alveolar type II cells","volume":"14","author":"Corti","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:19:27Z","timestamp":1771237167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041841"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041841","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]}}}