Redox regulation of wound healing? NF-kappa B activation in cultured humankeratinocytes upon wounding and the effect of low energy HeNe irradiation

The complex process of wound healing as well as the signaling systems orche strating this intricate process remain incompletely defined. Using human ke ratinocytes in primary culture, we sought to characterize their NF-kappa B responses to wounding alone or in combination with other treatments. We ini tially characterized these cultured human keratinocytes responses to known NF-kappa B activators (PMA, TNF-alpha and IL-1) using two different assays, immunohistochemistry and electrophoretic mobility shift (EMSA). After elic iting the expected NF-kappa B responses, we applied these same assays to as sess responses to either wounding or HeNe irradiation alone. The results ob tained indicated that only a modest/sporadic activation of NF-kappa B was e licited by these which was only detectable using immunohistochemistry. When the combination of wounding and HeNe irradiation on NF-kappa B status was assessed, a marked, localized activation of NF-kappa B in keratinocytes alo ng the wound edge was found. Treatment induced NF-kappa B activation (e.g., wounding, HeNe irradiation and combined wounding and HeNe irradiation) was abrogated by pyrrolidine dithiocarbamate (PDTC) which inhibits NF-kappa B activation through an as yet incompletely understood (antioxidant?) mechani sm. These data therefore suggest that NF-kappa B and oxidation mediated cha nges in its activation state likely play important roles in normal cutaneou s wound healing. (C) 1998 Elsevier Science Inc.