title: HIV-1 envelope protein gp120 up regulates CCL5 production in astrocytes which can be circumvented by inhibitors of NF-κB pathway.
abstract: HIV associated neurological disorders (HAND) is a common neurological complication in patients infected with HIV. The proinflammatory cytokines and chemokines produced by astrocytes play a pivotal role in neuroinflammatory processes in the brain and viral envelope gp120 has been implicated in this process. In view of increased levels of CCL5 observed in the CSF of HIV-1 infected patients, we studied the effects of gp120 on CCL5 expression in astrocytes and the possible mechanisms responsible for those effects. Transfection of the SVGA astrocyte cell line with a plasmid encoding gp120 resulted in a time-dependent increase in expression levels of CCL5 in terms of mRNA and protein by 24.6 ± 2.67- and 35.2 ± 6.1-fold, respectively. The fluorescent images showed localization of CCL5 in the processes of the astrocytes. The gp120-specific siRNA abrogated the gp120-mediated increase in CCL5 expression. We also explored a possible mechanism for the effects of gp120 on CCL5 expression. Using a specific inhibitor for the NF-κB pathway, we demonstrated that levels of gp120 induction of CCL5 expression can be abrogated by 44.6 ± 4.2% at the level of mRNA and 51.8 ± 5.0% at the protein level. This was further confirmed by knocking down NF-κB through the use of siRNA.
authors.affiliation: Division of Pharmacology and Toxicology, UMKC-School of Pharmacy, Kansas City, MO 64108, United States.
authors.forename: Ankit
authors.initials: A
authors.lastname: Shah
authors.forename: Dhirendra P
authors.initials: DP
authors.lastname: Singh
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013876:Thiophenes / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D034741:RNA, Small Interfering; C477523:SC 514; D013876:Thiophenes; C514793:gp120 protein, Human immunodeficiency virus 1