IL-18 and IL-12 signal through the NF-kappa B pathway to induce NK-1R expression on T cells.
Substance P engages the T cell neurokinin 1 receptor (NK-1R) to enhance IFN-gamma production. NK-1R on T cells is inducible. We studied mechanisms regulating T cell NK-1R expression. Murine splenocytes were cultured for 4 h with or without rIL-12 or rIL-18. Both IL-12 and IL-18 induced splenic T cells to express NK-1R transcripts. Induction was blocked by actinomycin D, but not cycloheximide, suggesting that protein synthesis was not required for initiation of NK-1R gene transcription. Inhibition of T cell NF-kappa B activation or NF-kappa B nuclear translocation also blocked NK-1R transcription. IL-12 and IL-18 strongly induce NK-1R mRNA expression in splenocytes from Stat4(-/-) mice, suggesting that the Stat4 pathway was not required for the induction of NK-1R transcription. Splenic T cells exposed to IL-12 or IL-18 in the presence of IL-10 expressed no NK-1R mRNA. However, TGF beta did not prevent NK-1R mRNA expression. Thus, IL-12 and IL-18 induce T cells to express NK-1R through NF-kappa B activation. IL-10, a regulator of the Th1 response, blocks this activation. These data further suggest that SP and NK-1R, which promote IFN-gamma synthesis, are part of the Th1 pathway of immunity.
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. joel-weinstock@uiowa.edu
Joel V
JV
Weinstock
Arthur
A
Blum
Ahmed
A
Metwali
David
D
Elliott
Razvan
R
Arsenescu
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
D020382:Interleukin-18; D016328:NF-kappa B; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12