title: TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.
abstract: This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-β-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.
authors.affiliation: Institute of Biomedicine (IBIOMED), University of León, Campus Universitario, 24071 León, Spain ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Rodrigo
authors.identifier: 0000-0003-2816-9855
authors.initials: R
authors.lastname: Fernandez-Gonzalo
authors.affiliation: Institute of Biomedicine (IBIOMED), University of León, Campus Universitario, 24071 León, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: De Paz
authors.affiliation: Institute of Biomedicine (IBIOMED), University of León, Campus Universitario, 24071 León, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Rodriguez-Miguelez
authors.affiliation: Institute of Biomedicine (IBIOMED), University of León, Campus Universitario, 24071 León, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Cuevas
authors.affiliation: Institute of Biomedicine (IBIOMED), University of León, Campus Universitario, 24071 León, Spain.
authors.forename: Javier
authors.identifier: 0000-0002-4386-9342
authors.initials: J
authors.lastname: González-Gallego
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D055815:Young Adult
chemical_list: D050838:Interferon Regulatory Factor-3; D053594:Myeloid Differentiation Factor 88; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA