title: Induction of IL-6 and IL-10 production by recombinant HIV-1 envelope glycoprotein 41 (gp41) in the THP-1 human monocytic cell line.
abstract: Elevated levels of circulating monokines (IL-6, IL-1, and TNF alpha) have been seen in HIV-1 infection, and the overproduction of these cytokines could contribute to AIDS pathogenesis in various ways. In previous work, we had seen that exposure of human monocytes to HIV-1, including inactivated, noninfectious HIV, led to rapid IL-6 gene expression and secretion. To investigate cytokine production in response to components of HIV by monocytes/macrophages, production of IL-6 and IL-10 were examined in a human monocytic cell line, THP-1, stimulated by HIV proteins. IL-6 production was induced in THP-1 cells by a detergent lysate of HIV, particularly fractions at molecular weight of 25-50 kDa. Recombinant HIV envelope glycoprotein 41 (gp41), but not gp120 or p24, also was seen to induce significant IL-6 production by THP-1 cells. These results suggest that gp41, transmembrane protein, is the primary HIV-encoded protein involved in inducing IL-6 production. IL-10 was also produced with delayed kinetics, following IL-6 production in THP-1 cells stimulated by gp41. To investigate a possible regulatory role for IL-10 in HIV-induced monokine production, recombinant IL-10 was added to gp41-exposed THP-1 cells. IL-10 inhibited gp41-induced IL-6 production and reduced the expression of IL-6 mRNA. When anti-human IL-10 neutralizing antibody was added to THP-1 cells, IL-6 production was enhanced. These results suggest that the IL-6 production may be downregulated by endogenously produced IL-10 and that IL-10 may downregulate cytokine production by HIV-activated monocytes via an autoregulatory mechanism.
authors.affiliation: UCLA School of Nursing, USA.
authors.forename: S
authors.initials: S
authors.lastname: Takeshita
authors.forename: E C
authors.initials: EC
authors.lastname: Breen
authors.forename: M
authors.initials: M
authors.lastname: Ivashchenko
authors.forename: P G
authors.initials: PG
authors.lastname: Nishanian
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: D L
authors.initials: DL
authors.lastname: Vredevoe
authors.forename: O
authors.initials: O
authors.lastname: Martinez-Maza
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D016655:HIV Core Protein p24 / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10