Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation
Open accessAbstract
Irisin, an adipomiokine known as a mediator of physical activity, induces the browning of adipose tissue and it has potentially protective properties in the development of obesity-related states, such as insulin resistance, arteriosclerosis, and type 2 diabetes. Despite numerous studies conducted on this factor, still little is known about its impact on the functioning of immunocompetent cells, but its potential anti-inflammatory properties were previously suggested. In the current study we investigated the role of irisin (0–100 nM) in the downstream pathway activation of Toll-like receptor 4 (TLR4) in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS; 100 ng/mL). The results have shown that irisin in high concentrations (50, 100 nM) significantly decreased the TLR4 and MyD88 protein levels, as well as the phosphorylation of nuclear factor-κB (NF-κB), consequently leading to the reduction in the release of crucial pro-inflammatory cytokines. The above was confirmed for interleukin 1β (IL-1β), tumor necrosis factor α (TNFα), interleukin 6 (IL-6), keratinocyte chemoattractant (KC), monocyte chemotactic protein 1 (MCP-1), as well as for high mobility group box 1 (HMGB1). Moreover, our results indicate that this effect is connected with irisin’s impact on the phosphorylation of mitogen-activated protein kinases (MAPKs), where a significant reduction in p-JNK and p-ERK but not p-p38 was observed. In conclusion, these data suggest that irisin has potentially anti-inflammatory properties connected with the downregulation of downstream pathways of TLR4/MyD88.
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In the short term, irisin might directly favor a shift from M1 to M2 phenotype, as well as decrease the expression of TLR4, TNF-α, IL-1β, MCP-1, and IL-6 by adipocytes and macrophages, while increasing IL-10 and antioxidant cellular mechanisms.
“As also shown in Figure 2 (to facilitate sequence flow, the steps appear numbered as they are introduced in the main text in italics), in the short term, irisin might directly favor a shift from M1 Mφ to a M2 phenotype [49,59], as well as decrease the expression of TLR4, TNF-α, IL-1β, MCP-1, and IL-6 by adipocytes and Mφ [51,53,59] (1a), while increasing IL-10 [59] (1b) and antioxidant cellular me”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [53]
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“Myokines myostatin↔ irisin [44,49] METRNL→ ↑irisin, BAIBA* [92,100] FGF21→ ↑irisin* [43] follistatin→ ↓myostatin [184] SeP→ ↓adiponectin [136], ↓irisin, BAIBA, METRNL (via ↓PGC-1α due to ↓OS)* [50] irisin→ ↑adiponectin [51], ?↓leptin [54,55] IL-15→↑adiponectin [86] BAIBA→ ↑leptin [109] irisin→ ↓TNF-α, IL-1β, IL-6, MCP…”
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- Authors
- Mazur-Bialy, A. I., Pocheć, E., & Zarawski, M.
- Affiliations
- Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531 Krakow, Poland
- Jagiellonian University (PL)
- Department of Gynecology and Obstetrics with Gynecologic Oncology, Rydygier Hospital Krakow, Zlotej Jesieni 1, 31-826 Krakow, Poland
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-03-25
- Volume
- 18
- Issue
- 4
- Pages
- 701
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5412287
- OpenAlex
- W2600882296
- Cited by
- 203
- References
- 44
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 19 · 2023: 33 · 2022: 32 · 2021: 30 · 2020: 22 · 2019: 16 · 2018: 12 · 2017: 3
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerstwo Nauki i Szkolnictwa Wyzszego (K/DSC/002108)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- irisin, anti-inflammatory activity, TLR4, MyD88, TLR4/MyD88 signaling, NF-κB phosphorylation, macrophages, lipopolysaccharide, inflammatory cytokines, HMGB1, MAPK phosphorylation, JNK, ERK, adipokines, obesity
- MeSH terms
- Animals, Cell Line, Fibronectins, Lipopolysaccharides, Macrophages, Tumor Necrosis Factor-alpha, Interleukin-6, NF-kappa B, Chemokine CCL2, MAP Kinase Signaling System, HMGB1 Protein, Toll-Like Receptor 4, Mice, Interleukin-1beta, Myeloid Differentiation Factor 88
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