MAPK signaling pathways modulate IL-1beta 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-1beta 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 SCC-12F.

Aryl hydrocarbon receptor-mediated posttranscriptional regulation of IL-1beta.

TCDD stimulated IL-1beta gene expression in differentiating human keratinocyte cell lines in a time- and dose-dependent manner. Increases in prointerleukin-1beta (pIL-1beta) protein and IL-1beta steady state mRNA levels were observed in both SCC-12F and HaCaT cells following TCDD treatment. When pretreated with alpha-naphthoflavone, an AhR antagonist, TCDD-mediated increases in IL-1beta gene expression were attenuated, demonstrating for the first time that the environmental toxin, TCDD, can stimulate cytokine (IL-1beta) gene expression in an AhR-dependent manner.