title: Expression of substance P, neurokinin-1 receptor and immune markers in the brains of individuals with HIV-associated neuropathology.
abstract: The tachykinin neuropeptide substance P (SP) has an important signaling role in both the nervous and the immune systems. Two naturally occurring variants of the neurokinin-1 receptor (NK1R) mediate the effects of SP, full-length receptor (NK1R-F) and a truncated form (NK1R-T) that lacks 96 amino acid residues at the C-terminus. We previously reported decreased expression of the NK1R-F in the CNS of HIV-positive individuals in comparison to HIV-negative control subjects. There were no differences in the expression of the NK1R-T in the same groups. In the current study, we quantified the expressions of SP precursor mRNA preprotachykinin (TAC1), NK1R (full and truncated forms), viral load (HIV-gag) and several proinflammatory and immune markers (CD4, CCR5, CXCR4, fractalkine, IL-6, IL-10, CCL2, CCL20 and CD163) in the frontal cortex of autopsied brains from HIV-1-positive individuals with or without HIV-associated neuropathology. The expressions of SP and, to lesser extent, NK1R-F were decreased while the expressions of CXCR4, CCR5 and CCL2 were increased in CNS of individuals with HIV-associated neuropathology. There was no change in HIV loads associated with neuropathology; however, we found a positive correlation between viral loads and the expression of haptoglobin-hemoglobin scavenger receptor CD163. An analysis of CSF from corresponding samples demonstrated an increase in proinflammatory markers (CCL2 MIP-1α and MIP-1β) associated with neuropathology. Although our data confirm the overall inflammatory nature of HIV-associated neuropathology, we observed a decrease in the expression of SP and NK1R-F, which is also associated with other forms of neuroinflammation.
authors.affiliation: Division of Allergy and Immunology, Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Spitsin
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Stevens
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis*; D013373:Substance P / Q000096:biosynthesis*; D019562:Viral Load; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D018040:Receptors, Neurokinin-1; D013373:Substance P
keywords: Brain; HIV; HIVE; Neurokinin-1 receptor; Neuropathology; Substance P
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