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dc.contributor.authorLavandoski, Patriciapt_BR
dc.contributor.authorLima, Vinícius Pierdonápt_BR
dc.contributor.authorMaurmann, Rafael Mourapt_BR
dc.contributor.authorGrun, Lucas Kichpt_BR
dc.contributor.authorGuma, Fátima Theresinha Costa Rodriguespt_BR
dc.contributor.authorTuana, Florencia María Barbépt_BR
dc.date.accessioned2023-11-18T03:25:11Zpt_BR
dc.date.issued2023pt_BR
dc.identifier.issn1664-3224pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/267229pt_BR
dc.description.abstractIntroduction: Eotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear. Therefore, the primary goal of this study was to explore the role of CCL11 on senescence development and the signaling pathways activated by this chemokine in lung fibroblasts. Methods: To investigate the targets potentially modulated by CCL11, we performed an in silico analysis using PseudoCell. We validated in vitro the activation of these targets in the human lung fibroblast cell line MRC-5 following rhCCL11 exposure. Finally, we performed differential gene expression analysis in human airway epithelial cells of asthmatic patients to assess CCL11 signaling and activation of additional senescent markers. Results: Our study revealed that eotaxin-1/CCL11 promote reactive oxygen secretion (ROS) production in lung fibroblasts, accompanied by increased activation of the DNA damage response (DDR) and p-TP53 and γH2AX. These modifications were accompanied by cellular senescence promotion and increased secretion of senescence-associated secretory phenotype inflammatory cytokines IL-6 and IL-8. Furthermore, our data show that airway epithelial lung cells from atopic asthmatic patients overexpress CCL11 along with aging markers such as CDKN2A (p16INK4a) and SERPINE1. Discussion: These findings provide new insights into the mechanisms underlying the pro-aging effects of CCL11 in the lungs of asthmatic patients. Understanding the role of CCL11 on senescence development may have important implications for the treatment of age-related lung diseases, such as asthma.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofFrontiers in immunology. Lausanne. Vol. 14 (Oct. 2023), 1243537, 13 p.pt_BR
dc.rightsOpen Accessen
dc.subjectCCL11en
dc.subjectDoenças respiratóriaspt_BR
dc.subjectEotaxin-1en
dc.subjectQuimiocina CCL11pt_BR
dc.subjectSenescenceen
dc.subjectPulmãopt_BR
dc.subjectFibroblastsen
dc.subjectFibroblastospt_BR
dc.subjectEnvelhecimentopt_BR
dc.subjectAsthmaen
dc.subjectSenescência celularpt_BR
dc.subjectPremature agingen
dc.subjectAsmapt_BR
dc.subjectLungen
dc.titleEotaxin-1/CCL11 promotes cellular senescence in human-derived fibroblasts through pro-oxidant and pro-inflammatory pathwayspt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001187390pt_BR
dc.type.originEstrangeiropt_BR


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