title: Transcriptional Regulation of CXCL5 in HIV-1-Infected Macrophages and Its Functional Consequences on CNS Pathology.
abstract: Human immunodeficiency virus-1 (HIV-1)-infected monocytes/macrophages and microglia release increased levels of proinflammatory cytokines and chemokines, including ELR+ (containing glutamic acid-leucine-arginine motif) chemokines. To investigate the role of HIV-1 infection on chemokine regulation, monocyte-derived macrophages (MDMs) from normal donors were infected with HIV-1 and the expression of chemokines and their downstream biological functions were evaluated. Among the tested chemokines, CXCL5 was upregulated significantly both at the mRNA and protein level in the HIV-1-infected MDMs compared with mock-infected cultures. Upregulation of CXCL5 in the HIV-1-infected MDMs is, in part, regulated by increased interleukin-1β (IL-1β) production and phosphorylation of ERK1/2. Functional analyses indicate that HIV-1-induced overexpression of CXCL5 has enhanced the ability to attract neutrophils, as observed by chemotaxis assay. However, exposure of NT2, SH-SY5Y cells, and primary neurons to HIV-1-infected MDM supernatants resulted in cell death that was not rescued by anti-CXCL5 antibody suggesting that CXCL5 does not have direct effect on neuronal death. Together, these results suggest that the increased level of CXCL5 in tissue compartments, including the central nervous system of HIV-1-infected individuals might alter the inflammatory response through the infiltration of neutrophils into tissue compartment, thus causing secondary effects on resident cells.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Debjani
authors.initials: D
authors.lastname: Guha
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Klamar
authors.forename: Todd
authors.initials: T
authors.lastname: Reinhart
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D020805:Central Nervous System Viral Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D054365:Chemokine CXCL5 / Q000235:genetics* / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D009474:Neurons / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D054365:Chemokine CXCL5; D018925:Chemokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta