Involvement of the Hsp70/TLR4/IL-6 and TNF-α pathways in delayed-onset muscle soreness.
Aerobiosis
Animals
HSP70 Heat-Shock Proteins
Interleukin-6
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal
/ metabolism
Myalgia
/ physiopathology
Myeloid Differentiation Factor 88
/ genetics
Pain Measurement
Physical Conditioning, Animal
Signal Transduction
Spinal Cord
/ metabolism
Toll-Like Receptor 4
/ antagonists & inhibitors
Tumor Necrosis Factor-alpha
DOMS
Hsp70
TLR4
cytokines
exercise
nociception
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
05
05
2019
revised:
09
03
2020
accepted:
12
03
2020
pubmed:
17
3
2020
medline:
11
2
2021
entrez:
17
3
2020
Statut:
ppublish
Résumé
Delayed-onset muscle soreness (DOMS) is a very common condition in athletes and individuals not accustomed to physical activity that occurs after moderate/high-intensity exercise sessions. The activation of microglial Toll-like receptor 4 (TLR4) in the spinal cord has been described to be important for the induction and maintenance of persistent pain. Based on that, we hypothesize that 70 kilodalton heat-shock protein (Hsp70), a mediator released by exercise, could activate microglial TLR4 in the spinal cord, releasing proinflammatory cytokines and contributing to the start of DOMS. In fact, we found that the knockout of TLR4, myeloid differentiation primary response 88 (MyD88), interleukin-6 (IL-6), or both tumor necrosis factor-α (TNF-α) receptor 1 and TNF-α receptor 2 in mice prevented the development of DOMS following acute aerobic exercise in contrast to the findings in male C57BL/6 wild-type mice. Furthermore, DOMS in exercised wild-type mice was also prevented after pre-treatment with microglia inhibitor, TLR4 antagonist, and anti-Hsp70 antibody. During exercise-induced DOMS, Hsp70 mRNA, TLR4 mRNA, and protein levels, as well as Iba-1 (a microglial marker), IL-6, and TNF-α protein levels, were increased in the muscle and/or spinal cord. Together, these findings suggest that Hsp70 released during exercise-induced DOMS activates the microglial TLR4/IL-6/TNF-α pathway in the spinal cord. Thus, the blockade of TLR4 activation may be a new strategy to prevent the development of DOMS before intense exercise.
Substances chimiques
HSP70 Heat-Shock Proteins
0
Interleukin-6
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Tumor Necrosis Factor-alpha
0
interleukin-6, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
29-44Informations de copyright
© 2020 International Society for Neurochemistry.
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