Cellular fibronectin is induced in ultraviolet-exposed human skin and induces IL-10 production by monocytes macrophages

CD11b(+) monocytic/macrophagic cells that infiltrate human skin after in vi vo ultraviolet exposure potently produce interleukin-10. We hypothesized th at binding of monocyte beta 1 integrins to ultraviolet-induced extracellula r matrix Ligands, such as fibronectin, after entry of blood monocytes into the dermis, is involved in the modulation of immunoregulatory monocytic cyt okines. Immunostaining of human skin and reverse transcriptase-polymerase c hain reaction studies revealed that the embryonic isoform of cellular fibro nectin, in which the extra domain A (EDA) segment is spliced in (EDA(+) cel lular fibronectin), and confers enhanced binding to beta 1 integrins, is ne wly induced and is associated with infiltrating CD11b(+) cells post in vivo ultraviolet exposure. We then tested the effect of fibronectin on resting purified peripheral monocytes in vitro. We found that monocyte interleukin- 10, but not interleukin-12, was significantly induced in a concentration-de pendent manner by in vitro binding to cellular fibronectin (n = 6), but not plasma fibronectin. Tumor necrosis factor-alpha was also induced in a conc entration-dependent manner, but to a lesser extent. Monoclonal antibodies t o beta 1 integrins beta-subunit (CD29) also strongly induced tumor necrosis factor-alpha and interleukin-10 production, but not interIeukin-12. Neutra lization of tumor necrosis factor-alpha reduced by 54% the interleukin-10 p roduction that was induced by monocytes binding to cellular fibronectin, in dicating that interleukin-10 induction is at least in part dependent upon c oncomitant autocrine tumor necrosis factor-alpha release. In conclusion, ul traviolet skin injury results in increased production and deposition of EDA (+) cellular fibronectin in the papillary dermis, which may be one of the k ey signals capable of inducing interleukin-10 but not interleukin-12 in mon ocytes that infiltrate micromilieu of human skin after ultraviolet exposure .