title: HDAC6 mediates HIV-1 tat-induced proinflammatory responses by regulating MAPK-NF-kappaB/AP-1 pathways in astrocytes.
abstract: Human immunodeficiency virus (HIV)-1 transactivator of transcription (Tat) is a viral protein that induces extensive neuroinflammation by up-regulating proinflammatory mediators, including cytokines, chemokines, and adhesion molecules. Histone deacetylase 6 (HDAC6) has been implicated in the transcriptional regulation of inflammatory genes. In this study, we investigated the possible role of HDAC6 in HIV-1 Tat-induced up-regulation of proinflammatory mediators in astrocytes. HIV-1 Tat augmented HDAC6 expression, which was correlated with a reduction in acetylated α-tubulin in CRT-MG human astroglioma cells and primary mouse astrocytes. Knockdown and pharmacological inhibition of HDAC6 significantly inhibited HIV-1 Tat-induced expression of CCL2, CXCL8, and CXCL10 chemokines; adhesion molecules; and subsequent adhesion of monocytes to astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced activation of mitogen-activated protein kinase species, including ERK, JNK, and p38. Furthermore, HDAC6 knockdown suppressed HIV-1 Tat-induced activation of NF-κB and AP-1. Thus, HDAC6 is involved in HIV-1 Tat-induced expression of proinflammatory genes by regulating mitogen-activated protein kinase-NF-κB/AP-1 pathways and serves as a molecular target for HIV-1 Tat-mediated neuroinflammation GLIA 2015;63:1953-1965.
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Youn
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Ju
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
keywords: HDAC6; HIV-1 Tat; MAPK; NF-κB; astrocyte; inflammation