TUMOR NECROSIS FACTOR IN REGENERATION OF DEEP SKIN WOUNDS IN MICE

Mechanisms of skin wound healing have been extensively studied in order to propose novel approaches for treatment of chronic and poorly healing wounds, including those associated with autoimmune pathologies, as well as for fibrosis prevention. Recent studies indicate the key role of proinfl ammatory cytokines, such as TNF, IL-6 and IL-1, in regulating skin regeneration. In our work we investigated the impact of tumor necrosis factor (TNF) on healing of deep skin wounds in mice by employing reverse genetics approach. We found, that conditional knock-out of TNF gene specifically in macrophages results in delayed wound healing. However inactivation of TNF in all cell types does not aff ect wound regeneration dynamics. Moreover, genetic knock-out of TNF receptor I (TNFRI) results in accelerated wound healing. Thus, the results of our study suggest that TNF from diff erent cell types plays a dual role in skin regeneration probably refl ecting that both cellular source of TNF as well as receptor type on target cells are important.

regeneration, deep skin wound, TNF, TNFRI, fibrosis, macrophages