Interleukin 6 Function in the Skin and Isolated Keratinocytes Is Modulated by Hyperglycemia.

Diabetes currently affects over twenty-five million Americans. Annual health care cost of diabetes exceeds $254 billion and is associated with a distinct set of diabetic complications that include delayed wound healing and diabetic ulcers. Interleukin 6 (IL-6) plays an important role in wound healing and is known to be elevated in the serum of both type I and type II diabetes patients.

IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis.

Contact dermatitis is the second most reported occupational injury associated with workers compensation. Inflammatory cytokines are closely involved with the development of dermatitis, and their modulation could exacerbate skin damage, thus contributing to increased irritancy. IL-6 is a pro-inflammatory cytokine paradoxically associated with both skin healing and inflammation.

Estrogen suppresses heptatic IκB expression during short-term alcohol exposure.

Objective: To assess the effects of sex steroids on hepatic inflammatory pathways in short-term chronically ethanol-fed rats.

Methods: Ovariectomized female Wistar rats (8-12 weeks old, n = 8 per treatment group) were implanted with osmotic pumps releasing 17β-estradiol (20 μg/24 h) or testosterone (25 μg/24 h) and fed liquid diets with or without ethanol (8 % w/v) for two weeks. Hepatic expression of IκBα/β, TNF-α, and IL-6 mRNA was examined by real-time PCR.

IL-6 modulates alpha-smooth muscle actin expression in dermal fibroblasts from IL-6-deficient mice.

IL-6 deficient (IL-6KO) mice display significantly delayed cutaneous wound closure. Myofibroblasts are the primary mediators of wound closure, and alpha-smooth muscle actin (alpha-SMA) is a marker of fibroblast differentiation to the myofibroblast phenotype. Wounds from IL-6KO, and wild-type mice were collected up to 6 days following wounding.

The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses.

A20 is a cytoplasmic protein required for the termination of tumor necrosis factor (TNF)-induced signals. We show here that mice doubly deficient in either A20 and TNF or A20 and TNF receptor 1 developed spontaneous inflammation, indicating that A20 is also critical for the regulation of TNF-independent signals in vivo. A20 was required for the termination of Toll-like receptor-induced activity of the transcription factor NF-kappaB and proinflammatory gene expression in macrophages, and this function protected mice from endotoxic shock.