title: Extracellular HIV-1 Tat induces human beta-defensin-2 production via NF-kappaB/AP-1 dependent pathways in human B cells.
abstract: Defensins, a family of antimicrobial peptides, are one of the first lines of host defense. Human beta-defensins (hBD) such as hBD-2 and -3 have anti-HIV activity. Previous studies have shown that HIV-1 virion can induce the expression of hBD, although the exact components of HIV-1 virion that are responsible for hBD expression have not yet been elucidated. In this study, we examined the effect of HIV-1 Tat on the expression of hBD in B cells. Stimulation of B cells with HIV-1 Tat protein significantly increased the mRNA and protein levels of hBD-2. HIV-1 Tat also induced the activation of a reporter gene for hBD-2 in a dose-dependent manner in B cells. Pretreatment of B cells with a JNK inhibitor suppressed HIV-1 Tat-induced hBD-2 expression. Pretreatment of B cells with AP-1 inhibitors or NF-κB inhibitors led to a decrease in HIV-1 Tat-induced protein and mRNA expression of hBD-2. Taken together, our results indicate that HIV-1 Tat can up-regulate the expression of hBD-2 via JNK-NF-κB/AP-1-dependent pathways in human B cells.
authors.affiliation: Department of Biomedical Science, Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Ju
authors.forename: Ah Ra
authors.initials: AR
authors.lastname: Goh
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Kwon
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Youn
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Bae
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D023083:beta-Defensins; D054322:tat Gene Products, Human Immunodeficiency Virus; D003609:Dactinomycin; D048369:MAP Kinase Kinase 1; D048670:MAP Kinase Kinase 4