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Up-Regulate Substance P Receptor Expression in Murine Peritoneal Macrophages1
Department of Biology, University of North Carolina, Charlotte, NC 28223
While the ability of macrophages to express authentic substance P
receptors (i.e., NK-1 receptors) has been inferred from radioreceptor
binding assays and functional assays and, most recently, by
identification of NK-1 receptor mRNA expression, we know little about
NK-1 expression at the protein level or what host factors might
up-regulate expression of this receptor. In the present study we
demonstrate that the cytokines IL-4 and IFN-
can increase the
expression of NK-1 receptors on murine peritoneal macrophages.
Specifically, we show that IL-4 and IFN-
can elicit increases in the
level of mRNA encoding the NK-1 receptor by up to 12- and 13-fold,
respectively. Furthermore, these cytokines can significantly increase
the expression of the NK-1 receptor protein as measured by Western blot
and FACS analysis using specific Abs developed in our laboratory. In
addition, we have demonstrated the ability of both IL-4 and IFN-
to
enhance the ability of macrophages to bind substance P as measured by
radiolabeled binding assay. The observation that the level of
expression of this receptor protein can be enhanced by cytokines that
promote either cell-mediated (Th1) or humoral (Th2) immune responses
supports the idea that this receptor can be induced during either type
of immune response. As such, these results may point to a more
ubiquitous role for substance P in the generation of optimal immune
responses than previously appreciated.
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