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Role of Interleukin-6 in Vascular Health and Disease
Open accessAbstract
IL-6 is usually described as a pleiotropic cytokine produced in response to tissue injury or infection. As a pro-inflammatory cytokine, IL-6 activates innate and adaptative immune responses. IL-6 is released in the innate immune response by leukocytes as well as stromal cells upon pattern recognition receptor activation. IL-6 then recruits immune cells and triggers B and T cell response. Dysregulated IL-6 activity is associated with pathologies involving chronic inflammation and autoimmunity, including atherosclerosis. However, IL-6 is also produced and released under beneficial conditions, such as exercise, where IL-6 is associated with the anti-inflammatory and metabolic effects coupled with physical adaptation to intense training. Exercise-associated IL-6 acts on adipose tissue to induce lipogenesis and on arteries to induce adaptative vascular remodeling. These divergent actions could be explained by complex signaling networks. Classical IL-6 signaling involves a membrane-bound IL-6 receptor and glycoprotein 130 (gp130), while trans-signaling relies on a soluble version of IL-6R (sIL-6R) and membrane-bound gp130. Trans-signaling, but not the classical pathway, is regulated by soluble gp130. In this review, we discuss the similarities and differences in IL-6 cytokine and myokine signaling to explain the differential and opposite effects of this protein during inflammation and exercise, with a special focus on the vascular system.
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“In APOE3Ch , IPA analysis indicated activation of anti‐angiogenic IL‐12 signaling, 47 along with predicted inactivation of IL‐6, an upstream regulator associated with inflammation, vascular activation, and coagulation. 48”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [48]
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Metadata
- Authors
- Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., Gabrielli, L., & Chiong, M.
- Affiliations
- Advanced Center for Chronic Diseases (CL)
- University of Chile (CL)
- Pontificia Universidad Católica de Chile (CL)
- Corresponding author
- Gabrielli, Luigi
- Chiong, Mario
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2021-03-16
- Volume
- 8
- Pages
- 641734-641734
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC8004548
- OpenAlex
- W3139260880
- Cited by
- 154
- References
- 154
- Citations by year
- 2026: 20 · 2025: 39 · 2024: 32 · 2023: 35 · 2022: 19 · 2021: 9
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Funders
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (1170963, 15130011)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- interleukin-6, vascular health, vascular disease, atherosclerosis, chronic inflammation, autoimmunity, physical activity, myokines, IL-6 signaling, trans-signaling, soluble IL-6 receptor, gp130, adipose tissue lipogenesis, vascular remodeling, innate and adaptive immunity
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