UVB‐irradiated human keratinocytes and interleukin‐1&agr; indirectly increase MAP kinase/AP‐1 activation and MMP‐1 production in UVA‐irradiated dermal fibroblasts

Xiao-Yong Wang,Zhi‐gang Bl

Published 2006 in Chinese Medical Journal

ABSTRACT

Background Solar ultraviolet (UV) irradiation induces the production of matrix metalloproteinases (MMPs) by activating cellular signalling transduction pathways. MMPs are responsible for the degradation and/or inhibition of synthesis of collagenous extracellular matrix in connective tissues. We mimicked the action of environmental ultraviolet on skin and investigated the effects of UVB‐irradiated human keratinocytes HaCaT and IL‐1&agr; on mitogen activated protein (MAP) kinase activation, c‐Jun and c‐Fos (AP‐1 is composed of Jun and Fos proteins) mRNA expression and MMP‐1 production in UVA‐irradiated dermal fibroblasts. Methods Following UVA irradiation, the culture medium of fibroblasts was replaced by culture medium from UVB‐irradiated HaCaT, or replaced by the complete culture medium with interleukin (IL)‐1&agr;. MAP kinase activity expression in fibroblasts was detected by Western blot. c‐Jun and c‐Fos mRNA expressions were determined by reverse transcriptional polymerase chain reaction (RT‐PCR); MMP‐1 production in culture medium was detected by enzyme‐linked immunosorbent assay (ELISA). Results Culture medium from UVB‐irradiated keratinocytes increased MAP kinase activity and c‐Jun mRNA expression in UVA‐irradiated fibroblasts. IL‐1&agr; increased MAP kinase activity and c‐Jun mRNA expression, IL‐1&agr; also increased c‐Fos mRNA expression. Both culture media from UVB‐irradiated human keratinocytes and externally applied IL‐1&agr; increased MMP‐1 production in UVA‐irradiated fibroblasts. Conclusions UVB‐irradiated keratinocytes and IL‐1&agr; indirectly promote MMP‐1 production in UVA‐irradiated fibroblasts by increasing MAP kinase/AP‐1 activity. IL‐1 may play an important role in the paracrine activation and dermal collagen excessive degradation leading to skin photoaging.

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