Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis

Ann N Y Acad Sci. 2008 Nov:1144:90-6. doi: 10.1196/annals.1418.007.


Substance P (SP) is upregulated in HIV infection in adult men and women, as determined by increased plasma levels. There is a reciprocal and bidirectional relationship between substance P and HIV in HIV-infected monocyte-derived macrophages and cell lines (e.g., THP-1). Substance P up-regulates HIV and HIV up-regulates SP protein expression. Neurokinin-1 receptor (NK1R) antagonists inhibit HIV infectivity through downregulation of the chemokine receptor, CCR5, and downregulation of HIV LTR. Neurokinin-1 receptor is expressed in full-length and truncated forms. The full-length NK1R is capable of signaling, whereas the truncated NK1R primes the chemokine receptor CCR5. Both full-length and truncated NK1R are expressed in several brain regions in human autopsy brains. SP-NK1R interactions have regulatory roles in inflammation and infection. The differential expression of truncated and full-length NK1R has important biological consequences. These include receptor-receptor interaction (e.g., NK1R-CCR5); changes in expression during cell differentiation (e.g., THP-1 cells); and differences in regional tissue distribution (e.g., differences in different brain regions). NK1R-SP receptor pathways are important cell regulatory pathways.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • Cell Differentiation
  • Cell Line
  • Down-Regulation
  • Female
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / pathology
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Neuroimmunomodulation
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism
  • Receptors, Neurokinin-1 / metabolism*
  • Signal Transduction
  • Substance P / metabolism


  • Anti-HIV Agents
  • Receptors, CCR5
  • Receptors, Neurokinin-1
  • Substance P