Interleukin 1β (IL1B) signaling is a critical component of radiation-induced skin fibrosis

Abstract Liu, W., Ding, I., Chen, K., Olschowka, J., Xu, J., Hu, D., Morrow, G. and Okunieff, P. Interleukin 1β (IL1B) Signaling is a Critical Component of Radiation-Induced Skin Fibrosis. Radiat. Res. 165, 181–191 (2006). Interleukin 1 beta (IL1B), a potent pro-inflammatory cytokine, is directly up-regulated by radiation and is known to regulate other inflammation-related molecules, such as the matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). However, the nature of the interaction of IL1B with MMPs and TIMPs in radiation-induced skin fibrosis is unknown. We examined the response of primary dermal keratinocytes, fibroblasts and endothelial cells to single-fraction radiation (10 Gy) and compared the results to a temporal sequence of histology from irradiated C57BL/6 and IL1R1 knockout mice. These studies showed that keratinocytes are the major IL1-producing cells in vitro and that radiation induces an immediate and chronic elevation in the expression of IL1B mRNA in the skin of C57...