{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:04:44Z","timestamp":1791605084447,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2013\/07467-1"],"award-info":[{"award-number":["2013\/07467-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["305414\/2019-4"],"award-info":[{"award-number":["305414\/2019-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["2013\/07467-1"],"award-info":[{"award-number":["2013\/07467-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["305414\/2019-4"],"award-info":[{"award-number":["305414\/2019-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb\/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg\/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2\/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE\/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.<\/jats:p>","DOI":"10.3390\/cells12060924","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T04:10:48Z","timestamp":1679026248000},"page":"924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-966X","authenticated-orcid":false,"given":"Carla","family":"Lima","sequence":"first","affiliation":[{"name":"Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICs\/FAPESP), Butantan Institute, S\u00e3o Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alice Pimentel","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICs\/FAPESP), Butantan Institute, S\u00e3o Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4207-940X","authenticated-orcid":false,"given":"Felipe Justiniano","family":"Pinto","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICs\/FAPESP), Butantan Institute, S\u00e3o Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson Thiago Gon\u00e7alves","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICs\/FAPESP), Butantan Institute, S\u00e3o Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lopes-Ferreira","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Laboratory of Applied Toxinology (CeTICs\/FAPESP), Butantan Institute, S\u00e3o Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0140-6736(17)33311-1","article-title":"Asthma","volume":"391","author":"Papi","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.chest.2019.10.009","article-title":"Recent Advances in Severe Asthma: From Phenotypes to Personalized Medicine","volume":"157","author":"Schoettler","year":"2020","journal-title":"Chest"},{"key":"ref_3","first-page":"118","article-title":"Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes","volume":"36","author":"Gans","year":"2020","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fmed.2020.00191","article-title":"Airway Remodeling in Asthma","volume":"7","author":"Hough","year":"2020","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"396","DOI":"10.2500\/aap.2019.40.4256","article-title":"Asthma in adults: Principles of treatment","volume":"40","author":"Kwah","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1164\/rccm.202109-2205PP","article-title":"Global Initiative for Asthma Strategy 2021 Executive Summary and Rationale for Key Changes","volume":"205","author":"Reddel","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","first-page":"334","article-title":"Current and Future Immunotherapies for Multiple Sclerosis","volume":"118","author":"Bourque","year":"2021","journal-title":"Sci. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Del Gatto, A., Saviano, M., and Zaccaro, L. (2021). An Overview of Peptide-Based Molecules as Potential Drug Candidates for Multiple Sclerosis. Molecules, 26.","DOI":"10.3390\/molecules26175227"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41573-020-00135-8","article-title":"Trends in Peptide Drug Discovery","volume":"20","author":"Muttenthaler","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"697586","DOI":"10.3389\/fmolb.2021.697586","article-title":"Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives","volume":"8","author":"Cabri","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_11","unstructured":"Lopes-Ferreira, M., Lima, C., Pimenta, D.C., Concei\u00e7\u00e3o, K., Demasi, M., and Portaro, F.C.V. (2007). Pept\u00eddeos C\u00edclicos Antiinflama\u00f3rios e Antial\u00e9rgicos WO2008009085A1: Monica Valdyrce Dos Anjos Lopes Ferreira, Crist\u00e1lia Produtos Qu\u00edmicos Farmac\u00eauticos Ltd.a, Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa Do Estado de S\u00e3o Paulo (FAPESP)."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Komegae, E.N., Souza, T.A.M., Grund, L.Z., Lima, C., and Lopes-Ferreira, M. (2017). Multiple Functional Therapeutic Effects of TnP: A Small Stable Synthetic Peptide Derived from Fish Venom in a Mouse Model of Multiple Sclerosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171796"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lima, C., Eto, S.F., and Lopes-Ferreira, M. (2022). Shedding Light on the Drug\u2013Target Prediction of the Anti-Inflammatory Peptide TnP with Bioinformatics Tools. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080994"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"857692","DOI":"10.3389\/fimmu.2022.857692","article-title":"TnP Peptide Suppresses Experimental Autoimmune Encephalomyelitis (EAE) in a Preclinical Mouse Model","volume":"13","author":"Lima","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.fsi.2021.04.029","article-title":"Knockdown of MiR-26a in Zebrafish Leads to Impairment of the Anti-Inflammatory Function of TnP in the Control of Neutrophilia","volume":"114","author":"Falcao","year":"2021","journal-title":"Fish Shellfish Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Disner, G.R., Falc\u00e3o, M.A.P., Lima, C., and Lopes-Ferreira, M. (2021). In Silico Target Prediction of Overexpressed MicroRNAs from Lps-Challenged Zebrafish (Danio Rerio) Treated with the Novel Anti-Inflammatory Peptide TnP. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137117"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.toxrep.2020.12.004","article-title":"Early Preclinical Screening Using Zebrafish (Danio Rerio) Reveals the Safety of the Candidate Anti-Inflammatory Therapeutic Agent TnP","volume":"8","author":"Maleski","year":"2021","journal-title":"Toxicol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Van Hulst, G., Bureau, F., and Desmet, C.J. (2021). Eosinophils as Drivers of Severe Eosinophilic Asthma: Endotypes or Plasticity?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810150"},{"key":"ref_19","first-page":"139","article-title":"Neutrophilic Inflammation in Asthma HHS Public Access","volume":"176","author":"Ray","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1248\/bpb.b19-00095","article-title":"Steroid-Resistant Asthma and Neutrophils","volume":"43","author":"Nabe","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1165\/rcmb.2010-0027TR","article-title":"Role of Transforming Growth Factor-\u03b2 in Airway Remodeling in Asthma","volume":"44","author":"Halwani","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.coi.2018.05.006","article-title":"Role of Neutrophils in Allergic Asthma","volume":"54","author":"Radermecker","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_23","first-page":"704","article-title":"Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients","volume":"55","author":"Shefrin","year":"2009","journal-title":"Can. Fam. Physician"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.4103\/jfmpc.jfmpc_1210_21","article-title":"Comparative effectiveness of oral dexamethasone vs. oral prednisolone for acute exacerbation of asthma: A randomized control trial","volume":"11","author":"Banoth","year":"2022","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1136\/archdischild-2020-320239","article-title":"Can Low-Dose Dexamethasone Be Used Instead of Prednisolone in Acute Asthma Attacks?","volume":"106","author":"Wallace","year":"2021","journal-title":"Arch. Dis. Child"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fang, L., Sun, Q., and Roth, M. (2020). Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030757"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and Mast Cells in Allergic Disease","volume":"18","author":"Galli","year":"2014","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The Cytokines of Asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"ref_29","first-page":"139","article-title":"Plasma IL6 Levels, Metabolic Dysfunction, and Asthma Severity: A Cross-Sectional Analysis of Two Cohorts","volume":"176","author":"Peters","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41582-020-00421-4","article-title":"Towards treating progressive multiple sclerosis","volume":"16","author":"Thompson","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.chest.2022.02.029","article-title":"Management of Life-Threatening Asthma","volume":"162","author":"Garner","year":"2022","journal-title":"Chest"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ovchinnikova, T.V. (2019). Structure, Function, and Therapeutic Potential of Marine Bioactive Peptides. Mar. Drugs, 17.","DOI":"10.3390\/md17090505"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Margelidon-Cozzolino, V., Tsicopoulos, A., Chenivesse, C., and de Nadai, P. (2022). Role of Th17 Cytokines in Airway Remodeling in Asthma and Therapy Perspectives. Front. Allergy, 3.","DOI":"10.3389\/falgy.2022.806391"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3389\/fphys.2012.00460","article-title":"Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment","volume":"3","author":"Brannan","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1042\/CS20191309","article-title":"Bidirectional interaction of airway epithelial remodeling and inflammation in asthma","volume":"134","author":"Banno","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.3389\/fimmu.2020.01134","article-title":"Biological Therapies of Severe Asthma and Their Possible Effects on Airway Remodeling","volume":"11","author":"Kardas","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1164\/rccm.201611-2248ST","article-title":"ATS Assembly on Respiratory Structure and Function. An Official American Thoracic Society Research Statement: Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling","volume":"195","author":"Prakash","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/6\/924\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:20Z","timestamp":1760122640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/6\/924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cells12060924"],"URL":"https:\/\/doi.org\/10.3390\/cells12060924","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}