title: HIV enhances substance P expression in human immune cells.
abstract: Substance P (SP), a potent modulator of neuroimmunoregulation, is expressed in human immune cells. We observed elevated plasma SP levels in HIV-infected men compared with uninfected subjects. In the present study, we investigated the possible cellular source of the increased SP level caused by HIV infection. Using real-time reverse transcriptase-polymerase chain reaction, we demonstrated that monocyte-derived macrophages (MDM) and lymphocytes from both placental cord blood and adult peripheral blood expressed SP mRNA, which was significantly increased by HIV infection. HIV-induced SP expression was positively related to virus replication in the infected MDM. Purified recombinant HIV envelope glycoprotein 120 (gp120) derived from both the macrophage-tropic strain (MN) and the T lymphocyte-tropic strain (IIIB), when added to MDM cultures, enhanced SP mRNA expression. The gp120-induced SP expression was abrogated by pretreating the cells with soluble CD4. Furthermore, the activation of HIV in the latently infected promonocytic cell line (U1) and T-cell line (ACH-2) up-regulated SP mRNA expression. These data support the hypothesis that interaction of HIV and SP may have significant in vivo relevance to the immunopathogenesis of HIV infection and AIDS.
authors.affiliation: The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D001769:Blood / Q000276:immunology; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013373:Substance P / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015533:Transcriptional Activation; D015854:Up-Regulation; D017735:Virus Latency
chemical_list: D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013373:Substance P