Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a c...
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| Veröffentlicht in: | International journal of molecular sciences 2023-07, Vol.24 (13), p.11049 |
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| creator | Simon, Karina Smidt Coelho, Luísa Coutinho Veloso, Jr, Paulo Henrique de Holanda Melo-Silva, Cesar Augusto Morais, José Athayde Vasconcelos Longo, João Paulo Figueiró Figueiredo, Florencio Viana, Leonora Silva Pereira, Ildinete Amado, Veronica Moreira Mortari, Marcia Renata Bocca, Anamelia Lorenzetti |
| description | Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF. |
| doi_str_mv | 10.3390/ijms241311049 |
| format | Article |
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Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms241311049</identifier><identifier>PMID: 37446227</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adjuvants ; Animal models ; Animals ; Apoptosis ; Bleomycin ; Collagen ; Collagen Type I ; Cytokines ; Disease ; Enzyme-linked immunosorbent assay ; Fibroblasts ; Fibrosis ; Gene expression ; Health aspects ; Idiopathic Pulmonary Fibrosis - drug therapy ; Idiopathic Pulmonary Fibrosis - pathology ; Immune response ; Immune system ; Immunomodulation ; Inflammation ; Lung - pathology ; Lung diseases ; Lungs ; Mice ; Mice, Inbred C57BL ; Morphology ; Peptides ; Peptides - pharmacology ; Peptides - therapeutic use ; Pulmonary fibrosis ; Respiratory function ; Respiratory system</subject><ispartof>International journal of molecular sciences, 2023-07, Vol.24 (13), p.11049</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-821b306603bebbece1d4c90ad38ba08d096fc4d571f8948d69abb2277072b9383</citedby><cites>FETCH-LOGICAL-c483t-821b306603bebbece1d4c90ad38ba08d096fc4d571f8948d69abb2277072b9383</cites><orcidid>0000-0003-3067-4842 ; 0000-0002-3544-6999 ; 0000-0003-3323-5300 ; 0000-0003-2395-7748 ; 0000-0002-5154-7263 ; 0000-0002-6849-6001 ; 0000-0003-1403-9363</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341510/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341510/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37446227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Simon, Karina Smidt</creatorcontrib><creatorcontrib>Coelho, Luísa Coutinho</creatorcontrib><creatorcontrib>Veloso, Jr, Paulo Henrique de Holanda</creatorcontrib><creatorcontrib>Melo-Silva, Cesar Augusto</creatorcontrib><creatorcontrib>Morais, José Athayde Vasconcelos</creatorcontrib><creatorcontrib>Longo, João Paulo Figueiró</creatorcontrib><creatorcontrib>Figueiredo, Florencio</creatorcontrib><creatorcontrib>Viana, Leonora</creatorcontrib><creatorcontrib>Silva Pereira, Ildinete</creatorcontrib><creatorcontrib>Amado, Veronica Moreira</creatorcontrib><creatorcontrib>Mortari, Marcia Renata</creatorcontrib><creatorcontrib>Bocca, Anamelia Lorenzetti</creatorcontrib><title>Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. 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Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.</description><subject>Adjuvants</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Bleomycin</subject><subject>Collagen</subject><subject>Collagen Type I</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>Idiopathic Pulmonary Fibrosis - drug therapy</subject><subject>Idiopathic Pulmonary Fibrosis - pathology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Lung - pathology</subject><subject>Lung diseases</subject><subject>Lungs</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Morphology</subject><subject>Peptides</subject><subject>Peptides - 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Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37446227</pmid><doi>10.3390/ijms241311049</doi><orcidid>https://orcid.org/0000-0003-3067-4842</orcidid><orcidid>https://orcid.org/0000-0002-3544-6999</orcidid><orcidid>https://orcid.org/0000-0003-3323-5300</orcidid><orcidid>https://orcid.org/0000-0003-2395-7748</orcidid><orcidid>https://orcid.org/0000-0002-5154-7263</orcidid><orcidid>https://orcid.org/0000-0002-6849-6001</orcidid><orcidid>https://orcid.org/0000-0003-1403-9363</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adjuvants Animal models Animals Apoptosis Bleomycin Collagen Collagen Type I Cytokines Disease Enzyme-linked immunosorbent assay Fibroblasts Fibrosis Gene expression Health aspects Idiopathic Pulmonary Fibrosis - drug therapy Idiopathic Pulmonary Fibrosis - pathology Immune response Immune system Immunomodulation Inflammation Lung - pathology Lung diseases Lungs Mice Mice, Inbred C57BL Morphology Peptides Peptides - pharmacology Peptides - therapeutic use Pulmonary fibrosis Respiratory function Respiratory system |
| title | Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis |
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