MAPK signaling pathways modulate IL-1β expression in human keratinocytes

The signaling pathways that modulate IL-1beta expression in human keratinocytes have not been well defined. We have previously shown that TCDD-stimulated AhR-dependent IL-10 expression in human keratinocytes is due to posttranscriptional regulation involving mRNA stabilization. Since TCDD activates a variety of cellular signaling pathways such as PKC, JNK, and ERK, we investigated these pathways to determine their roles in TCDD-stimulated IL-1beta expression in the human keratinocyte cell line SCG 12F. In this study, we used specific signaling inhibitors to show that ERK and JNK, but not transglutaminase, PKC, or p38, signaling modulate IL-1beta expression. In addition, we show that ERK is constitutively active and unaffected by TCDD treatment and differentiation, while the JNK signaling pathway is modulated by TCDD in an AhR-dependent manner. Thus, both the ERK and JNK MAPK pathways are necessary for IL-1beta expression in TCDD-stimulated human keratinocytes, however, they act at different levels to modulate IL-1beta expression. (C) 2004 Elsevier Inc. All rights reserved.