Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis
Title | Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Douglas, SD, Lai, JP, Tuluc, F, Schwartz, L, Kilpatrick, LE |
Journal | Annals of the New York Academy of Sciences |
Volume | 1144 |
Pagination | 90-96 |
Date Published | 2008 |
Keywords | CCR5, External, Neurokinin-1, Receptors |
Abstract | 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. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/19076368 |