Regulation of β‐Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines

Astrocytes constitute a part of the blood–brain barrier. Chemokine expression by astrocytes may contribute to leucocyte infiltration within the central nervous system (CNS) during inflammation. To investigate factor(s) regulating chemokine expression by astrocytes, we studied the induction of β‐chemokine mRNA expression in adult rat astrocytes. Astrocyte‐derived monocyte chemoattractant protein‐1 (MCP‐1), RANTES, macrophage inflammatory protein (MIP)‐1α and MIP‐1β mRNA were induced by interferon‐γ (IFN‐γ). Tumour necrosis factor‐α (TNF‐α) induced MCP‐1, RANTES and MIP‐1β mRNA expression, and lipopolysaccharide (LPS) induced MCP‐1, MIP‐1α and MIP‐1β mRNA expression in astrocytes. LPS‐induced MCP‐1, MIP‐1α and MIP‐1β mRNA expression by astrocytes was antagonized by transforming growth factor (TGF)‐β1 and interleukin (IL)‐10. TGF‐β1 and IL‐10 also down‐regulated MCP‐1 and RANTES mRNA expression induced by TNF‐α. IL‐10, but not TGF‐β1, inhibited MIP‐1β mRNA expression induced by TNF‐α. The results of this in vitro study suggest that β‐chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF‐β1 and IL‐10, down‐regulate astrocyte‐derived β‐family chemokine mRNA expression induced by LPS, IFN‐γ and TNF‐α. Further study of CNS chemokines will enhance our understanding of leucocyte recruitment to the CNS and suggest therapeutic strategies for neurological disorders.

[1]  R. Ransohoff,et al.  Do chemokines mediate leukocyte recruitment in post-traumatic CNS inflammation? , 1998, Trends in Neurosciences.

[2]  M. Kitamura,et al.  Identification of an inhibitor targeting macrophage production of monocyte chemoattractant protein-1 as TGF-beta 1. , 1997, Journal of immunology.

[3]  M. Mehler,et al.  Hematolymphopoietic and inflammatory cytokines in neural development , 1997, Trends in Neurosciences.

[4]  Y. Inoue,et al.  Identification of cell types producing RANTES, MIP-1α and MIP-1β in rat experimental autoimmune encephalomyelitis by in situ hybridization , 1997, Journal of Neuroimmunology.

[5]  A. Sauter,et al.  Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: effects of ischemia and peripheral lipopolysaccharide administration , 1997, Journal of Neuroimmunology.

[6]  T. Molitor,et al.  Differential production of and migratory response to beta chemokines by human microglia and astrocytes. , 1997, The Journal of infectious diseases.

[7]  R. Ransohoff,et al.  Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. , 1997, The American journal of pathology.

[8]  E. Benveniste,et al.  Induction of RANTES expression by astrocytes and astrocytoma cell lines , 1996, Journal of Neuroimmunology.

[9]  S. Rotshenker,et al.  Deficient activation of microglia during optic nerve degeneration , 1996, Journal of Neuroimmunology.

[10]  B. Trapp,et al.  Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes. , 1996, The Journal of clinical investigation.

[11]  R. Ransohoff,et al.  Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. , 1996, Journal of immunology.

[12]  D. Taub,et al.  Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice. , 1996, Journal of immunology.

[13]  D. Taub,et al.  Chemokines and T lymphocyte activation: I. Beta chemokines costimulate human T lymphocyte activation in vitro. , 1996, Journal of immunology.

[14]  G. Graham,et al.  Specificity and reciprocity in the interactions between TGF-beta and macrophage inflammatory protein-1 alpha. , 1996, Journal of immunology.

[15]  G. Nuovo,et al.  Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Ransohoff,et al.  Central Nervous System Chemokine mRNA Accumulation Follows Initial Leukocyte Entry at the Onset of Acute Murine Experimental Autoimmune Encephalomyelitis , 1995, Brain, Behavior, and Immunity.

[17]  R. Strieter,et al.  An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis. , 1995, Journal of immunology.

[18]  M. Hart,et al.  TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. , 1995, Journal of immunology.

[19]  B. Gesser,et al.  Regulation of human T lymphocyte chemotaxis in vitro by T cell-derived cytokines IL-2, IFN-gamma, IL-4, IL-10, and IL-13. , 1995, Journal of immunology.

[20]  S. Kikuchi,et al.  Macrophage inflammatory protein-1 alpha in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases. , 1995, Journal of the neurological sciences.

[21]  A. Hurwitz,et al.  Tumor necrosis factor α and transforming growth factor β upregulate astrocyte expression of monocyte chemoattractant protein-1 , 1995, Journal of Neuroimmunology.

[22]  T. Olsson,et al.  Organ‐specific autoantigens induce interferon‐γ and interleukin‐4 mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis , 1994, Neurology.

[23]  D. Taub,et al.  Preferential migration of activated CD4+ and CD8+ T cells in response to MIP-1 alpha and MIP-1 beta , 1993, Science.

[24]  C. Brosnan,et al.  Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. , 1991, The Journal of clinical investigation.

[25]  D. Goeddel,et al.  Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES , 1990, Nature.

[26]  T. Ewing.  First strike over pay and conditions , 1990, Nature.

[27]  E. Benveniste,et al.  Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. , 1990, Journal of immunology.

[28]  J. Kuratsu,et al.  Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants , 1989, The Journal of experimental medicine.

[29]  M. Cuzner,et al.  Characterisation of microglia isolated from adult human and rat brain , 1988, Journal of Neuroimmunology.

[30]  U. Traugott.  Multiple sclerosis: relevance of Class I and Class II MHC-expressing cells to lesion development , 1987, Journal of Neuroimmunology.

[31]  D. Silberberg,et al.  MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by γ-interferon , 1987, Journal of Neuroimmunology.

[32]  W. Fierz,et al.  Astrocytes present myelin basic protein to encephalitogenic T-cell lines , 1984, Nature.

[33]  G. Wong,et al.  Inducible expression of H–2 and Ia antigens on brain cells , 1984, Nature.