IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells

Joel V. Weinstock, Arthur Blum, Ahmed Metwali, David Elliott, Razvan Arsenescu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Substance P engages the T cell neurokinin 1 receptor (NK-1R) to enhance IFN-γ 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-κB activation or NF-κB 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, TGFβ did not prevent NK-1R mRNA expression. Thus, IL-12 and IL-18 induce T cells to express NK-1R through NF-κB activation. IL-10, a regulator of the Th1 response, blocks this activation. These data further suggest that SP and NK-1R, which promote IFN-γ synthesis, are part of the Th1 pathway of immunity.

Original languageEnglish (US)
Pages (from-to)5003-5007
Number of pages5
JournalJournal of Immunology
Volume170
Issue number10
StatePublished - May 15 2003
Externally publishedYes

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Neurokinin-1 Receptors
Interleukin-18
Interleukin-12
T-Lymphocytes
Interleukin-10
Messenger RNA
Dactinomycin
Cycloheximide
Substance P
Immunity

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Weinstock, J. V., Blum, A., Metwali, A., Elliott, D., & Arsenescu, R. (2003). IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells. Journal of Immunology, 170(10), 5003-5007.
Weinstock, Joel V. ; Blum, Arthur ; Metwali, Ahmed ; Elliott, David ; Arsenescu, Razvan. / IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells. In: Journal of Immunology. 2003 ; Vol. 170, No. 10. pp. 5003-5007.
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Weinstock, JV, Blum, A, Metwali, A, Elliott, D & Arsenescu, R 2003, 'IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells', Journal of Immunology, vol. 170, no. 10, pp. 5003-5007.

IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells. / Weinstock, Joel V.; Blum, Arthur; Metwali, Ahmed; Elliott, David; Arsenescu, Razvan.

In: Journal of Immunology, Vol. 170, No. 10, 15.05.2003, p. 5003-5007.

Research output: Contribution to journalArticle

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T1 - IL-18 and IL-12 signal through the NF-κB pathway to induce NK-1R expression on T cells

AU - Weinstock, Joel V.

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