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.
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.