title: Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation.
abstract: 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.
authors.affiliation: Department of Ergonomics and Exercise Physiology, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531 Krakow, Poland. agnieszka.mazur@uj.edu.pl.
authors.forename: Agnieszka Irena
authors.initials: AI
authors.lastname: Mazur-Bialy
authors.affiliation: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland. ewa.pochec@uj.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pocheć
authors.affiliation: Department of Gynecology and Obstetrics with Gynecologic Oncology, Rydygier Hospital Krakow, Zlotej Jesieni 1, 31-826 Krakow, Poland. mzarawski@gmail.com.
authors.forename: Marcin
authors.initials: M
authors.lastname: Zarawski
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005353:Fibronectins; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: adipomiokine; inflammation; irisin; leukocytes; macrophages; physical exercise; sport