Down-regulation of macrophage CD9 expression by interferon-gamma.
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-gamma, IFN-gamma. 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-gamma 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-gamma treatment. These results represent the first evidence for the down regulation of CD9 expression with macrophage activation.
Wang
Xue-Qing
XQ
Division of Cardiovascular Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Evans
Glenn F
GF
Alfaro
M Leticia
ML
Zuckerman
Steven H
SH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor; D060245:Tetraspanin 29; D015534:Trans-Activators / Q000502:physiology
D015703:Antigens, CD; C554870:Cd9 protein, mouse; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D060245:Tetraspanin 29; D015534:Trans-Activators; D007371:Interferon-gamma