title: Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.
abstract: Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Thangavel
authors.initials: T
authors.lastname: Samikkannu
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Kurapati V K
authors.initials: KV
authors.lastname: Rao
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Raymond
authors.affiliation: Department of Biostatistics, Robert Stempel College of Public Health and Social Work, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Changwon
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, United States of America.
authors.forename: Madhavan P N
authors.initials: MP
authors.lastname: Nair
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000097:blood*; D002478:Cells, Cultured; D003042:Cocaine / Q000009:adverse effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D015232:Dinoprostone / Q000097:blood; D055030:Drug Users; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000097:blood; D000071876:Prostaglandin-E Synthases
chemical_list: C477819:15-deoxyprostaglandin J2; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D003042:Cocaine; D015232:Dinoprostone; D015230:Prostaglandin D2