Abstract
CD11b+ monocytic/macrophagic cells that infiltrate human skin after in vivo ultraviolet exposure potently produce interleukin-10. We hypothesized that binding of monocyte beta1 integrins to ultraviolet-induced extracellular matrix ligands, such as fibronectin, after entry of blood monocytes into the dermis, is involved in the modulation of immunoregulatory monocytic cytokines. Immunostaining of human skin and reverse transcriptase-polymerase chain reaction studies revealed that the embryonic isoform of cellular fibronectin, in which the extra domain A (EDA) segment is spliced in (EDA+ cellular fibronectin), and confers enhanced binding to beta1 integrins, is newly 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-dependent manner by in vitro binding to cellular fibronectin (n = 6), but not plasma fibronectin. Tumor necrosis factor-alpha was also induced in a concentration-dependent manner, but to a lesser extent. Monoclonal antibodies to beta1 integrins beta-subunit (CD29) also strongly induced tumor necrosis factor-alpha and interleukin-10 production, but not interleukin-12. Neutralization of tumor necrosis factor-alpha reduced by 54% the interleukin-10 production that was induced by monocytes binding to cellular fibronectin, indicating that interleukin-10 induction is at least in part dependent upon concomitant autocrine tumor necrosis factor-alpha release. In conclusion, ultraviolet skin injury results in increased production and deposition of EDA+ cellular fibronectin in the papillary dermis, which may be one of the key signals capable of inducing interleukin-10 but not interleukin-12 in monocytes that infiltrate micromilieu of human skin after ultraviolet exposure.
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