Neurotensin enhances nitric oxide generation via the JAK2-STAT1 pathway in murine macrophage Raw264.7 cells during costimulation with LPS and IFNγ

Hyeon Soo Kim, Sanatombi Yumkham, Jang Hyun Choi, Sun Hee Lee, Tae Ho Kim, Sung Ho Ryu, Pann Ghill Suh

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Neurotensin has been known to be implicated in immune function, but its molecular mechanisms remain largely unclear. In this study, we report that neurotensin increased the intracellular calcium levels of murine macrophage Raw264.7 cells, and that this calcium increase disappeared in the presence of either U73122, a PLC inhibitor, or SR48692, a neurotensin receptor antagonist. Also, the production of nitric oxide (NO) during costimulation with lipopolysaccharide (LPS) and interferon gamma (IFNγ) was potentiated by exposure to neurotensin, whereas neurotensin itself had no ability to induce NO generation. The up-regulation of NO generation was correlated with the induction of inducible NO synthase (iNOS). In addition, the activities of janus activated kinase 2 (JAK2)-signal transducer and activated transcription 1 (STAT1) and the migration capacity of macrophage were increased as the result of costimulation of neurotensin with LPS and IFNγ, and pretreatment of either U73122 or SR48692 attenuated these phenomenon. Moreover, the neurotensin-mediated enhancement of NO generation and migration were observed in the wild-type JAK2 transfected cells, but not in the dominant negative JAK2 transfected cells. Together, these results demonstrate that neurotensin can effect enhancement in LPS/IFNγ-induced NO generation and migration capacity, via the JAK2-STAT1 pathway.

Original languageEnglish
Pages (from-to)221-229
Number of pages9
JournalNeuropeptides
Volume40
Issue number3
DOIs
Publication statusPublished - 2006 Jun 1
Externally publishedYes

Keywords

  • Calcium
  • Interferon gamma (IFNγ)
  • Janus activated kinase (JAK)
  • Lipopolysaccharide (LPS)
  • Neurotensin
  • Signal transducer and activated transcription (STAT)

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Neurology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Biochemistry

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