Eotaxin-1/CCL11 promotes cellular senescence in human-derived fibroblasts through pro-oxidant and pro-inflammatory pathways
Open accessAbstract
Introduction: 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.
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CCL11/Eotaxin1 is a chemokine that selectively recruits eosinophils, is elevated with age in humans and mice, and promotes senescence.
“CCL11/Eotaxin1 is a chemokine that selectively recruits eosinophils, is elevated with age in humans and mice52–54, and has been shown to promote senescence55.”
From Senescent-like microglia limit remyelination through the senescence associated secretory phenotype (2025) · cites this paper as [55]
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- Authors
- Lavandoski, P., Pierdoná, V., Maurmann, R. M., Grun, L. K., Guma, F. T. C. R., & Barbé-Tuana, F. M.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2023-10-04
- Volume
- 14
- Pages
- 1243537-1243537
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC10582634
- OpenAlex
- W4387340994
- Cited by
- 34
- References
- 46
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 11
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
- Universidade Federal do Rio Grande do Sul
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- cellular senescence, chemokines, reactive oxygen species, DNA damage response, TP53, γH2AX, senescence-associated secretory phenotype, interleukin-6, interleukin-8, airway epithelial cells, asthma, aging, lung fibroblasts, p16INK4a, SERPINE1
- MeSH terms
- Aged, Asthma, Child, Fibroblasts, Humans, Lung, Cellular Senescence, Reactive Oxygen Species, Chemokine CCL11
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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