title: Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes.
abstract: HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes.
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors: Gi Soo
authors: GS
authors: Youn
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors: Dong-Joo
authors: DJ
authors: Kwon
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors: Sung Mi
authors: SM
authors: Ju
authors: Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors: Hyangshuk
authors: H
authors: Rhim
authors: Department of Biological Science, College of Natural Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Yong Soo
authors: YS
authors: Bae
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors: Soo Young
authors: SY
authors: Choi
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: jinpark@hallym.ac.kr.
authors: Jinseu
authors: J
authors: Park
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D018808:Transcription Factor AP-1; D014315:Triterpenes; D054322:tat Gene Products, Human Immunodeficiency Virus; D051547:Heme Oxygenase-1; C050414:celastrol
keywords: AP-1; Astrocyte; HO-1; Inflammation; NF-κB; Tat