Immune Netw.  2011 Aug;11(4):223-226. 10.4110/in.2011.11.4.223.

IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling

• Lee WJ

• KMID: 1449814
• DOI: http://doi.org/10.4110/in.2011.11.4.223

Abstract

Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF-kappaB-target genes such as TNF-alpha and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway.

Keyword

Insulin-like growth factor-I; Toll-like receptor-4; Cytokines; Skeletal muscle cells; PI3K/Akt; MAPK

MeSH Terms

Cytokines
Down-Regulation
Insulin-Like Growth Factor I
Intercellular Signaling Peptides and Proteins
Interleukin-6
Muscle, Skeletal
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
Cytokines
Insulin-Like Growth Factor I
Intercellular Signaling Peptides and Proteins
Interleukin-6
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1 (A) Effect of different concentrations of IGF-I on TLR4 protein expression in differentiating C2C12 skeletal muscle cells. Cells were treated with IGF-I for 24 hr. (B) TLR4 protein expression in C2C12 cells treated with IGF-I (200 ng/ml) for 24 hr in the absence or presence of LY294002 (100µM) and Wortmannin (50 nM). (C) Cells were treated with IGF-I (200 ng/ml)+PD98059 (0.1 or 1.0 µM) for 24 hr. (D) Cells were treated with IGF-I (200 ng/ml)+SB203580 (0.1 or 1.0 µM) for 24 hr.

• 

  Figure 2 (A) TLR4 mRNA expression determined by real-time PCR in C2C12 myotubes cultured for 24 hr with different concentration of IGF-I. Effect of LY294002 (B), Wortmannin (C), SB203580 (D), or PD98059 (E) on IGF-I-mediated TLR4 expression. (F) The mRNA expression level of IL-6 and TNF-α in C2C12 cells cultured for 24 hr in the absence or presence of IGF-I (200 ng/ml). Target mRNA values are normalized to the GAPDH mRNA level for each sample. Samples were analyzed in duplicate in parallel with GAPDH. Values are menas±SE of three independent experiments. *p<0.05 vs. Control.

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