Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis.
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.
Douglas
Steven D
SD
Division of Allergy and Immunology, Joseph Stokes Jr Research Institute at the Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. DOUGLAS@email.chop.edu
Lai
Jian-Ping
JP
Tuluc
Florin
F
Schwartz
Lynnae
L
Kilpatrick
Laurie E
LE
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D015213:Neuroimmunomodulation; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D015398:Signal Transduction; D013373:Substance P / Q000378:metabolism
D019380:Anti-HIV Agents; D019713:Receptors, CCR5; D018040:Receptors, Neurokinin-1; D013373:Substance P