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Int. J. Mol. Sci. 2017, 18(4), 701;

Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation

Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531 Krakow, Poland
Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland
Department of Gynecology and Obstetrics with Gynecologic Oncology, Rydygier Hospital Krakow, Zlotej Jesieni 1, 31-826 Krakow, Poland
Author to whom correspondence should be addressed.
Academic Editors: Paula Andrade and Patrícia Valentão
Received: 31 January 2017 / Revised: 16 March 2017 / Accepted: 21 March 2017 / Published: 25 March 2017
(This article belongs to the Special Issue Natural Anti-Inflammatory Agents)
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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. View Full-Text
Keywords: physical exercise; irisin; adipomiokine; macrophages; inflammation; sport; leukocytes physical exercise; irisin; adipomiokine; macrophages; inflammation; sport; leukocytes

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Mazur-Bialy, A.I.; Pocheć, E.; Zarawski, M. Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation. Int. J. Mol. Sci. 2017, 18, 701.

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