HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Heat stroke activates a stress-induced cytokine response in skeletal muscle.

Abstract
Heat stroke (HS) induces a rapid elevation in a number of circulating cytokines. This is often attributed to the stimulatory effects of endotoxin, released from damaged intestine, on immune cells. However, parenchymal cells also produce cytokines, and skeletal muscle, comprising a large proportion of body mass, is thought to participate. We tested the hypothesis that skeletal muscle exhibits a cytokine response to HS that parallels the systemic response in conscious mice heated to a core temperature of 42.4°C (TcMax). Diaphragm and hindlimb muscles showed a rapid rise in interleukin-6 (IL-6) and interleuin-10 (IL-10) mRNA and transient inhibition of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) throughout early recovery, a pattern that parallels changes in circulating cytokines. IL-6 protein was transiently elevated in both muscles at ∼32 min after reaching TcMax. Other responses observed included an upregulation of toll-like receptor-4 (TLR-4) and heat shock protein-72 (HSP-72) mRNA but no change in TLR-2 or HSP25 mRNA. Furthermore, c-jun and c-fos mRNA increased. Together, c-jun/c-fos form the activator protein-1 (AP-1) transcription factor, critical for stress-induced regulation of IL-6. Interestingly, a second "late-phase" (24 h) cytokine response, with increases in IL-6, IL-10, IL-1β, and TNF-α protein, were observed in hindlimb but not diaphragm muscle. These results demonstrate that skeletal muscle responds to HS with a distinct "stress-induced immune response," characterized by an early upregulation of IL-6, IL-10, and TLR-4 and suppression of IL-1β and TNF-α mRNA, a pattern discrete from classic innate immune cytokine responses.
AuthorsSteven S Welc, Thomas L Clanton, Shauna M Dineen, Lisa R Leon
JournalJournal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 115 Issue 8 Pg. 1126-37 (Oct 15 2013) ISSN: 1522-1601 [Electronic] United States
PMID23928112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cytokines
  • Heat-Shock Proteins
  • IL10 protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
Topics
  • Animals
  • Cytokines (genetics, metabolism)
  • Disease Models, Animal
  • Gene Expression Regulation
  • Heat Stroke (genetics, immunology, metabolism)
  • Heat-Shock Proteins (genetics, metabolism)
  • Inflammation Mediators (metabolism)
  • Interleukin-10 (genetics, metabolism)
  • Interleukin-1beta (genetics, metabolism)
  • Interleukin-6 (genetics, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal (immunology, metabolism)
  • RNA, Messenger (metabolism)
  • Signal Transduction
  • Time Factors
  • Toll-Like Receptor 4 (genetics, metabolism)
  • Transcription Factors (genetics, metabolism)
  • Tumor Necrosis Factor-alpha (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: