title: Interleukin (IL)-4 inhibits phorbol-ester induced HIV-1 expression in chronically infected U1 cells independently from the autocrine effect of endogenous tumour necrosis factor-alpha, IL-1beta, and IL-1 receptor antagonist.
abstract: The anti-inflammatory cytokine interleukin 4 (IL-4) has shown both inductive and inhibitory effects on the replication of the human immunodeficiency virus type 1 (HIV-1) in primary CD4+ T cells and mononuclear phagocytes. In this study, IL-4 did not induce virus production, but inhibited phorbol esters (PMA)-stimulated HIV expression in chronically infected promonocytic U1 cells. This effect, however, was not accounted for by a decreased secretion of endogenous TNF-alpha induced by phorbol myristate acetate (PMA). We also observed that PMA upregulated the production of both IL-1beta and of IL-1 receptor antagonist (IL-1ra). IL-4 inhibited the secretion of IL-1beta and strongly increased that of IL-1ra; however, these effects were not responsible of IL-4-mediated inhibition of PMA-induced HIV expression since anti-IL-1ra antibodies did not revert IL-4 mediated suppression. U1 cells were transiently transfected with both wild-type (WT) long terminal repeat (LTR) constructs, or with LTR plasmids containing deletions of either the NF-kappaB or the Sp-1 binding sites. IL-4 inhibited LTR-driven transcription triggered by PMA stimulation of U1 cells, and this effect was dependent upon intact NF-kappaB but not Sp-1 binding sites. Thus, IL-4 may favour a state of microbiological quiescence in infected monocytic cells bypassing the induction of HIV expression mediated by pro-inflammatory cytokines.
authors.affiliation: Italian National Institute of Infectious Diseases Lazzaro Spallanzani, Roma, Italy. d.goletti@tiscali.it
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.forename: Audrey L
authors.initials: AL
authors.lastname: Kinter
authors.forename: Eliana M
authors.initials: EM
authors.lastname: Coccia
authors.forename: Angela
authors.initials: A
authors.lastname: Battistini
authors.forename: Nicola
authors.initials: N
authors.lastname: Petrosillo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D015536:Down-Regulation; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010957:Plasmids / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010703:Phorbol Esters; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D015500:Chloramphenicol O-Acetyltransferase