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Shedding of CD163, a Novel Regulatory Mechanism for a Member of the Scavenger Receptor Cysteine-Rich Family

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Abstract

The glucocorticoid-inducible transmembrane protein CD163 is a member of the scavenger receptor cysteine-rich (SRCR) family which is expressed exclusively on human monocytes and macrophages. The expression of the protein is significantly downregulated in response to phorbol 12-myristate 13-acetate (PMA) by a yet unknown mechanism. We now demonstrate that PMA induces shedding of a soluble form of CD163 rather than internalization, revealing a novel regulatory mechanism for a member of the SRCR family. Bisindolylmaleimide I was shown to inhibit phorbol ester-induced shedding, thus implying an involvement of protein kinase C (PKC). Furthermore, cleavage could be prevented by protease inhibitors. Therefore, we suggest that PMA-induced activation of PKC leads to protease-mediated shedding of CD163. These results indicate a specific release mechanism of soluble CD163 by human monocytes which could play an important role in modulating inflammatory processes.

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      CD163 is seen as a marker of differentiation in the macrophage lineage and its best studied role is binding of hemoglobin-haptoglobin complexes [12–14]. Similar to sTWEAK, CD163 can also be shed from cells and change into a soluble form [15]. The function of sCD163 remains mostly unclear.

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    Abbreviations used: SRCR, scavenger receptor cysteine-rich; PMA, phorbol 12-myristate 13-acetate; PKC, protein kinase C; FP, Fluticasone-17-propionate; BIM, bisindolylmaleimide

    1

    To whom correspondence should be addressed at Institut für Experimentelle Dermatologie, Von-Esmarch-Str. 56, 48149 Münster, Germany. Fax: +49 251 835 6549. E-mail:[email protected].

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