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Publication : Skeletal muscle fibers play a functional role in host defense during sepsis in mice.

First Author  Laitano O Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  7316
PubMed ID  33795743 Mgi Jnum  J:308298
Mgi Id  MGI:6707263 Doi  10.1038/s41598-021-86585-5
Citation  Laitano O, et al. (2021) Skeletal muscle fibers play a functional role in host defense during sepsis in mice. Sci Rep 11(1):7316
abstractText  Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO), and followed male and female mice at 6 and 12 h after peritoneal injection of cecal slurry (CS), a model of polymicrobial sepsis. Because of a previously identified increase in mortality to CS injection, males received ~ 30% lower dose. At 12 h, skmMyd88KO caused significant reductions in a wide variety of pro- and anti-inflammatory plasma cytokines, e.g. TNFalpha, IL-1beta and IL-10, compared to strain-matched controls in both males and females. Similar reductions were observed at 6 h in females. SkmMyd88KO led to ~ 40-50% elevations in peritoneal neutrophils at 6 and 12 h post CS in females. At 12 h post CS, skmMyd88KO increased peritoneal monocytes/macrophages and decreased %eosinophils and %basophils in females. SkmMyd88KO also led to significantly higher rates of mortality in female mice but not in males. In conclusion, the results suggest that skeletal muscle Myd88-dependent signal transduction can play functionally important role in normal whole body, innate immune inflammatory responses to peritoneal sepsis.
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