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Time‐course analysis of injured skeletal muscle suggests a critical involvement of ERK1/2 signaling in the acute inflammatory response
Author(s) -
Szelenyi Eric r.,
Urso Maria l.
Publication year - 2012
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.22323
Subject(s) - phosphorylation , skeletal muscle , kinase , p38 mitogen activated protein kinases , mapk/erk pathway , signal transduction , inflammation , phosphatase , medicine , microbiology and biotechnology , protein kinase a , endocrinology , cytokine , biology
The coupling and timing of pro‐ and anti‐inflammatory processes in skeletal muscle injury is poorly understood. We investigated the temporal response and regulated processes of extracellular signal–regulated kinases 1 and 2 (ERK1/2), p38, and IkappaB kinase (IKK) α/β signaling pathways after traumatic injury. Methods: Traumatic freeze injury was delivered to the tibialis anterior (TA) muscle in C57BL/6J mice, and injured and uninjured TA muscles were analyzed 3–72 h into the recovery period. Results: Significant increases in pro‐inflammatory cytokine transcription accompanied IKKβ phosphorylation, robust ERK pathway activation, and reduced heat shock protein (Hsp) protein expression at 3–24 h. At 24 h, ERK activation was abolished concomitantly with a significant increase in mitogen‐activated protein kinase phosphatase‐1 (MKP‐1). After 24 h, cytokine transcription along with ERK1/2 and IKKβ phosphorylation remained suppressed, whereas Hsp protein expression rose to significant levels by 72 h and associated with IKKβ. Conclusions: Results indicate a bimodal regulation of ERK1/2 in acute inflammation in which it is supportive from 3 to 24 h, and suppressive from 24 to 72 h. Muscle Nerve, 2012