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

The signaling pathways that modulate IL-1β expression in human keratinocytes have not been well defined. We have previously shown that TCDD-stimulated AhR-dependent IL-1β 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-1β expression in the human keratinocyte cell line SCC-12F. In this study, we used specific signaling inhibitors to show that ERK and JNK, but not transglutaminase, PKC, or p38, signaling modulate IL-1β 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-1β expression in TCDD-stimulated human keratinocytes, however, they act at different levels to modulate IL-1β expression.