Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance.

Interleukin-6 (IL-6) plays a paradoxical role in inflammation and metabolism. The pro-inflammatory effects of IL-6 are mediated via IL-6 "trans-signaling," a process where the soluble form of the IL-6 receptor (sIL-6R) binds IL-6 and activates signaling in inflammatory cells that express the gp130 but not the IL-6 receptor. Here we show that trans-signaling recruits macrophages into adipose tissue (ATM).

Interleukin-6 attenuates insulin-mediated increases in endothelial cell signaling but augments skeletal muscle insulin action via differential effects on tumor necrosis factor-alpha expression.

Objective: The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS). We hypothesized that IL-6 promotes endothelial cell signaling and capillary recruitment in vivo, contributing to increased glucose uptake.

Research Design And Methods: The effect of IL-6 with and without insulin on AMPK, insulin, and eNOS signaling in and nitric oxide (NO) release from human aortic endothelial cells (HAECs) was examined.

Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPARalpha and UCP2 expression in rats.

Chronic elevations in interleukin (IL)-6 have been associated with insulin resistance, but acute IL-6 administration can enhance insulin sensitivity. Our aim was to exogenously administer IL-6 to rats to elicit either chronic or repeated acute elevations in systemic IL-6. We hypothesized that a continuous elevation of IL-6 would inhibit glucose tolerance and insulin sensitivity while acute intermittent elevations would improve it.

FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle.

The mammalian target of rapamycin (mTOR) is regulated by growth factors to promote protein synthesis. In mammalian skeletal muscle, the Forkhead-O1 transcription factor (FOXO1) promotes catabolism by activating ubiquitin-protein ligases. Using C2C12 mouse myoblasts that stably express inducible FOXO1-ER fusion proteins and transgenic mice that specifically overexpress constitutively active FOXO1 in skeletal muscle (FOXO(++/+)), we show that FOXO1 inhibits mTOR signaling and protein synthesis.

Gene expression profiles of TNF-alpha, TACE, furin, IL-1beta and matrilysin in UVA- and UVB-irradiated HaCat cells.

Background/purpose: It is known that solar ultraviolet (UV) irradiation exerts multiple effects on mammalian skin tissues, one of which is the induction of local and systemic immunosuppression as well as inflammation. Tumor necrosis factor-alpha (TNF-alpha) and other cytokines are suggested to play a role in these responses. Quantitative real-time polymerase chain reaction (TaqMan RTPCR) was used to elucidate the effect of UVA and UVB irradiation on the expression of genes coding for TNF-alpha, IL-1beta, IL-10, FasL, matrilysin, TACE and furin in HaCaT cells over a 48 h period (IL-1beta, interleukin-1beta; FasL, Fas ligand).