title: Interleukin-1beta stimulates macrophage inflammatory protein-1alpha and -1beta expression in human neuronal cells (NT2-N).
abstract: Chemokines are important mediators in immune responses and inflammatory processes of neuroimmunologic and infectious diseases. Although chemokines are expressed predominantly by cells of the immune system, neurons also express chemokines and chemokine receptors. We report herein that human neuronal cells (NT2-N) produce macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha and MIP-1beta), which could be enhanced by interleukin (IL)-1beta at both mRNA and protein levels. The addition of supernatants from human peripheral blood monocyte-derived macrophage (MDM) cultures induced MIP-1beta mRNA expression in NT2-N cells. Anti-IL-1beta antibody removed most, but not all, of the MDM culture supernatant-induced MIP-1beta mRNA expression in NT2-N cells, suggesting that IL-1beta in the MDM culture supernatants is a major factor in the induction of MIP-1beta expression. Investigation of the mechanism(s) responsible for IL-1beta-induced MIP-1alpha and -1beta expression demonstrated that IL-1beta activated nuclear factor kappa B (NF-kappaB) promoter-directed luciferase activity in NT2-N cells. Caffeic acid phenethyl ester, a potent and specific inhibitor of activation of NF-kappaB, not only blocked IL-1beta-induced activation of the NF-kappaB promoter but also decreased IL-1beta-induced MIP-1alpha and -1beta expression in NT2-N cells. These data suggest that NF-kappaB is at least partially involved in the IL-1beta-mediated action on MIP-1alpha and -1beta in NT2-N cells. IL-1beta-mediated up-regulation of beta-chemokine expression may have important implications in the immunopathogenesis of inflammatory diseases in the CNS.
authors.affiliation: Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute of The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lai
authors.forename: David E
authors.initials: DE
authors.lastname: Pleasure
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Marge
authors.initials: M
authors.lastname: Williams
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D015846:Monokines / Q000096:biosynthesis / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor