Iwahashi H, et al. - This is the first investigation identifying a mechanism by which ultraviolet B (UVB) exposure induces a loss of Endo 180 (alias MRC2/uPARAP/CD280) with a specific focus on the crosstalk between keratinocytes and fibroblasts. Utilizing mRNA expression, protein levels and collagen internalization by quantitative RT-PCR, ELISA, and flow cytometry, respectively, Endo180 from normal human dermal fibroblasts, which were cultured with a conditioned medium (CM) of UVB-exposed keratinocytes, was examined. While Endo180 was not reduced by UVB irradiation to fibroblasts, the CM of UVB-exposed keratinocytes reduced Endo180 in fibroblasts. Collagen internalization into the fibroblasts was reduced and was linked to a loss of Endo180. Among cytokines secreted from UVB-exposed keratinocytes, IL-1α only decreased Endo180, and the reduction caused by the CM of UVB-exposed keratinocytes was removed by the presence of IL-1RA. Such findings show that a substance secreted from UVB-exposed keratinocytes regulates Endo180 expression and that IL-1α can play an essential role in the maintenance of Endo180.