title: Interactions between HIV-infected monocyte-derived macrophages and human brain microvascular endothelial cells result in increased expression of CC chemokines.
abstract: The presence of perivascular monocytic infiltration is a major hallmark of HIV-1-associated dementia. Since CC chemokines are chemoattractant cytokines that are able to attract T cells and monocytes/macrophages to sites of inflammation, and since infiltrating monocytes/macrophages remain in close contact with the brain endothelium, we investigated whether interactions between HIV-1-infected macrophages and brain endothelium result in an altered chemokine production. We found an increased mRNA expression of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and RANTES by macrophages after HIV-1 infection. Interactions between HIV-infected macrophages and brain microvascular endothelial cells resulted in an additional upregulation of chemokine mRNA expression, during cell-cell contact as well as in a trans-well system. Since IL-1 beta can function as a modulator of chemokine expression we investigated if interleukin-1 beta could be involved in the regulation of chemokine induction. Coculturing of HIV-infected macrophages and endothelial cells resulted in immune-activation as indicated by increased mRNA expression of IL-1 beta. Subsequently, addition of a neutralizing antibody against IL-1 beta resulted in altered chemokine expression by macrophages, but not by endothelial cells. Thus, IL-1 beta appears to play a major role in the regulation of chemokines during cellular interactions in HIV-associated dementia, but other factors may also be involved.
authors.affiliation: Eijkman-Winkler Institute, University Medical Center Utrecht, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: Boven
authors.forename: J
authors.initials: J
authors.lastname: Middel
authors.forename: E C
authors.initials: EC
authors.lastname: Breij
authors.forename: D
authors.initials: D
authors.lastname: Schotte
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: C
authors.initials: C
authors.lastname: Soderland
authors.forename: H S
authors.initials: HS
authors.lastname: Nottet
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D015870:Gene Expression / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D008833:Microcirculation / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000032:analysis; D012995:Solubility
chemical_list: D000906:Antibodies; D016375:Antisense Elements (Genetics); D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger