Contribution of IL-6 to the Hsp72, Hsp25, and αβ-crystallin responses to inflammation and exercise training in mouse skeletal and cardiac muscle

Abstract

The heat shock proteins (Hsps) Hsp72, Hsp25, and αβ-crystallin (αβC) may protect tissues during exercise and/or inflammatory insults; however, no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25, and αβC protein through an IL-6-dependent mechanism. We compared Hsp72, Hsp25, αβC, and IL-6 protein levels 4 h after systemic inflammation induced by lipopolysaccharide (LPS) in skeletal and cardiac muscles of wild-type (IL-6^+/+) and IL-6 deficient (IL-6^−/−) mice after 2 wk of RW or normal cage activity (Sed). LPS significantly increased skeletal Hsp72 and Hsp25 relative to saline in Sed IL-6^+/+, but not IL-6^−/−mice. LPS increased Hsp72 relative to saline in Sed IL-6^+/+cardiac muscle. RW increased basal Hsp72, Hsp25, and αβC in skeletal muscle in IL-6^+/+and IL-6^−/−mice. However, LPS was not associated with increases in any Hsp in RW IL-6^+/+or IL-6^−/−mice. LPS increased IL-6 protein in skeletal muscle and plasma in Sed and RW groups, with a significantly greater response in RW. The major results provide the first in vivo evidence that the absence of IL-6 is associated with reduced skeletal muscle Hsp72 and Hsp25 responses to LPS, but that IL-6 is not required for exercise-induced Hsp upregulation in skeletal or cardiac muscle.