Abstract
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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.