title: Macrophage inflammatory protein-2 and KC induce chemokine production by mouse astrocytes.
abstract: Astrocytes are specialized cells of the CNS that are implicated in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis. In acute and relapsing-remitting experimental allergic encephalomyelitis, the neutrophil chemoattractant CXC chemokines macrophage-inflammatory protein (MIP)-2 and KC are associated with reactive astrocytes in the parenchyma. In vitro treatment of primary astrocyte cultures with nanomolar concentrations of MIP-2 or KC markedly up-regulated expression of the monocyte/T cell chemoattractants monocyte chemoattractant protein-1, inflammatory protein-10, and RANTES by a mechanism that includes stabilization of mRNA. Production of TNF-alpha and IL-6 transcripts were also noted, as was autocrine induction of MIP-2 and KC message. In addition, low levels of MIP-1alpha and MIP-1beta were induced following treatment with MIP-2 or KC. These effects are specific to astrocytes as MIP-2 treatment of microglial cells failed to elicit chemokine production. The astrocyte chemokine receptor for MIP-2 has 2.5 nM affinity for ligand. Astrocytes from CXCR2-deficient mice still respond to KC and MIP-2, indicating the presence of an alternative or novel high affinity receptor for these ligands. We propose that this KC/MIP-2 chemokine cascade may contribute to the persistence of mononuclear cell infiltration in demyelinating autoimmune diseases.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: F R
authors.initials: FR
authors.lastname: Fischer
authors.forename: W W
authors.initials: WW
authors.lastname: Hancock
authors.forename: M E
authors.initials: ME
authors.lastname: Dorf
mesh_terms: D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology*; D019743:Chemokines, CXC; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis; D012074:Remission Induction; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D011500:Protein Synthesis Inhibitors; D023063:Receptors, Interleukin-8B; C074302:keratinocyte-derived chemokines; D003513:Cycloheximide