IL-4 and IFN-gamma up-regulate substance P receptor expression in murine peritoneal macrophages.
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-gamma can increase the expression of NK-1 receptors on murine peritoneal macrophages. Specifically, we show that IL-4 and IFN-gamma 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-gamma 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.
Marriott
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Department of Biology, University of North Carolina, Charlotte 28223, USA.
Bost
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D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002645:Chickens; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D007106:Immune Sera / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007457:Iodine Radioisotopes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013373:Substance P / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D007106:Immune Sera; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015847:Interleukin-4; D013373:Substance P; D007371:Interferon-gamma