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Histone deacetylase (HDAC) inhibitors have been demonstrated to regulate myeloid cell differentiation. In the present study the effects of the HDAC inhibitor trichostatin A (TSA) on the tetraspanin cell surface antigen CD9 were determined in primary murine macrophages. TSA inhibited CD9 protein and message expression and was optimal by 48 h. TSA did not induce similar effects on other surface markers and resulted in a modest increase or no effect on CD54 and CD11b, respectively. These effects were concentration dependent and concomitant with increased histone H4 acetylation. While interferon-γ (IFN-γ) and TSA had similar effects on CD9 expression, transcriptional profiling demonstrated significant differences in the genes activated by these stimuli. Notably CD14 message was down-regulated by IFN-γ while increased by TSA. These results demonstrate that HDAC inhibition may modulate macrophage function in part through changes in the expression of membrane proteins associated with matrix interactions. [Copyright &y& Elsevier]

CD9, a member of the tetraspanin family is a cell surface marker expressed on myeloid and nonmyeloid as well as on neoplastic cells. The present study has focused on the role of inflammation and macrophage activation in the regulation of CD9 expression. We report that the expression of CD9 on primary cultures of murine peritoneal macrophages was down regulated by Interferon-γ, IFN-γ. This down regulation was concentration-dependent and maximal by 48 h. The changes in surface expression were consistent with similar reductions in CD9 protein and message levels by Western and Northern blot analyses. The mechanism by which IFN-γ decreases CD9 expression appears to be through the Stat1 signaling pathway as Stat1 knockout mice did not demonstrate any reduction in CD9 expression by IFN-γ treatment. These results represent the first evidence for the down regulation of CD9 expression with macrophage activation. [Copyright &y& Elsevier]