Gamma Interferon‐Induced Nitric Oxide Production in Mouse CD5+ B1‐Like Cell Line and Its Association with Apoptotic Cell Death

The in vitro effect of gamma interferon (IFN‐γ) on nitric oxide (NO) production in a mouse CD5+ B1‐like cell line, TH2.52, was studied. The TH2.52 cell line is the hybridoma line between mouse B lymphoma line and mouse splenic B cells and expresses a series of B1 markers. IFN‐γ induced a marked NO production in TH2.52 cells through the expression of an inducible type of NO synthase (iNOS). IFN‐γ‐induced NO production was triggered by the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway since it was inhibited by AG490, a JAK2 inhibitor. The growth of TH2.52 cells significantly was inhibited in the presence of IFN‐γ. A significant number of cells underwent apoptotic cell death, accompanied by the DNA fragmentation, annexin V binding, and caspase 3 activation. N(G)‐monomethyl‐L‐arginine, an iNOS inhibitor, prevented IFN‐γ‐induced cell death. Therefore, IFN‐γ‐induced NO production was possible in causing cell death in TH2.52 cells. Further, IFN‐γ‐induced NO production and cell death significantly were prevented by interleukin‐4, a representative Th2 cytokine. The immunological significance of IFN‐γ‐induced NO production in a mouse B1‐like cell line is discussed.

[1]  M. M. Mu,et al.  Change of Mouse CD5+ B1 Cells to a Macrophage-Like Morphology Induced by Gamma Interferon and Inhibited by Interleukin-4 , 2002, Clinical and Vaccine Immunology.

[2]  S. Kaufmann,et al.  Immune responses to intracellular bacteria. , 2001, Current opinion in immunology.

[3]  M. M. Mu,et al.  Inhibition of Caspase 3 Abrogates Lipopolysaccharide-Induced Nitric Oxide Production by Preventing Activation of NF-κB and c-Jun NH2-Terminal Kinase/Stress-Activated Protein Kinase in RAW 264.7 Murine Macrophage Cells , 2001, Infection and Immunity.

[4]  N. Koide,et al.  Mouse B1 cell line responds to lipopolysaccharide via membrane-bound CD14 , 2001, Journal of endotoxin research.

[5]  V. Nguyen,et al.  IL-4-Activated STAT-6 Inhibits IFN-γ-Induced CD40 Gene Expression in Macrophages/Microglia1 , 2000, The Journal of Immunology.

[6]  C. Bogdan,et al.  The role of nitric oxide in innate immunity , 2000, Immunological reviews.

[7]  K. M. Rao,et al.  MOLECULAR MECHANISMS REGULATING iNOS EXPRESSION IN VARIOUS CELL TYPES , 2000, Journal of toxicology and environmental health. Part B, Critical reviews.

[8]  W. Cowden,et al.  Our shifting understanding of the role of nitric oxide in autoimmune encephalomyelitis: a review , 1999, Journal of Neuroimmunology.

[9]  D. Bredt.  Endogenous nitric oxide synthesis: biological functions and pathophysiology. , 1999, Free radical research.

[10]  B. Brüne,et al.  Nitric oxide (NO): an effector of apoptosis , 1999, Cell Death and Differentiation.

[11]  M. A. Borrello,et al.  Fibroblast-secreted macrophage colony-stimulating factor is responsible for generation of biphenotypic B/macrophage cells from a subset of mouse B lymphocytes. , 1999, Journal of immunology.

[12]  U. Schindler,et al.  Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Titheradge.  Nitric oxide in septic shock. , 1999, Biochimica et biophysica acta.

[14]  D. Gold,et al.  Nitric oxide in interstitial nephritis and other autoimmune diseases. , 1999, Seminars in nephrology.

[15]  N. Koide,et al.  Role of Nitric Oxide in Lipopolysaccharide-Induced Hepatic Injury in d-Galactosamine-Sensitized Mice as an Experimental Endotoxic Shock Model , 1999, Infection and Immunity.

[16]  A. Porter,et al.  Emerging roles of caspase-3 in apoptosis , 1999, Cell Death and Differentiation.

[17]  E. Santiago,et al.  The role of nitric oxide in the pathogenesis of multiple sclerosis. , 1998, Journal of physiology and biochemistry.

[18]  B. Brüne,et al.  Nitric oxide and its role in apoptosis. , 1998, European journal of pharmacology.

[19]  Y. Ohmori,et al.  IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. , 1997, Journal of immunology.

[20]  A. Malik,et al.  In vivo inhibition of nuclear factor-kappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. , 1997, Journal of immunology.

[21]  G M Cohen,et al.  Caspases: the executioners of apoptosis. , 1997, The Biochemical journal.

[22]  A. Zeiher,et al.  Nitric oxide and apoptosis: another paradigm for the double-edged role of nitric oxide. , 1997, Nitric oxide : biology and chemistry.

[23]  K. Kröncke,et al.  Nitric oxide: cytotoxicity versus cytoprotection--how, why, when, and where? , 1997, Nitric oxide : biology and chemistry.

[24]  J. Román,et al.  Inhibition of apoptotic cell death in B-CLL by interferon gamma correlates with clinical stage. , 1996, Leukemia.

[25]  J S Beckman,et al.  Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. , 1996, The American journal of physiology.

[26]  M. A. Borrello,et al.  Fibroblasts support outgrowth of splenocytes simultaneously expressing B lymphocyte and macrophage characteristics. , 1995, Journal of immunology.

[27]  P. Casali,et al.  B‐1 Cellular Origin and VH Segment Structure of IgG, IgA, and IgM Anti‐DNA Autoantibodies in Patients with Systemic Lupus Erythematosus a , 1995, Annals of the New York Academy of Sciences.

[28]  R. Seder.  Acquisition of lymphokine-producing phenotype by CD4+ T cells. , 1994, The Journal of allergy and clinical immunology.

[29]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[30]  D. Alling,et al.  Induction of differentiation in a B lymphoma X B lymphocyte hybrid line. II. Intraclonal heterogeneity in growth, secretion of IgM, and cytokine production in response to lipopolysaccharide. , 1993, Journal of immunology.

[31]  D. Campana,et al.  Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia , 1993, The Journal of experimental medicine.

[32]  M. Apicella,et al.  The primary B cell response to the O/core region of bacterial lipopolysaccharide is restricted to the Ly-1 lineage. , 1991, Journal of immunology.

[33]  R. Lisak,et al.  The frequency of CD5+ B lymphocytes in the peripheral blood of patients with myasthenia gravis , 1990, Neurology.

[34]  L. Arnold,et al.  Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes , 1988, The Journal of experimental medicine.

[35]  J. Kearney,et al.  Induction of germ-line anti-alpha 1-3 dextran antibody responses in mice by members of the Enterobacteriaceae family. , 1985, Journal of immunology.

[36]  W. Leiserson,et al.  Establishment of B cell hybridomas with B cell surface antigens. , 1982, Journal of immunology.

[37]  S. Tannenbaum,et al.  Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. , 1982, Analytical biochemistry.

[38]  Seaver,et al.  Nitric oxide as a secretory product of mammalian cells , 2004 .

[39]  V. Nguyen,et al.  IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia. , 2000, Journal of immunology.

[40]  C. Nathan,et al.  Nitric oxide and macrophage function. , 1997, Annual review of immunology.

[41]  J. Ihle.  The Janus protein tyrosine kinase family and its role in cytokine signaling. , 1995, Advances in immunology.

[42]  H. Magazine.  Detection of endothelial cell-derived nitric oxide: current trends and future directions. , 1995, Advances in neuroimmunology.

[43]  W. Paul,et al.  Acquisition of lymphokine-producing phenotype by CD4+ T cells. , 1994, Annual review of immunology.

[44]  P. Casali,et al.  Autoimmunity-prone B-1 (CD5 B) cells, natural antibodies and self recognition. , 1993, Autoimmunity.

[45]  K. Rajewsky,et al.  Expansion and functional activity of Ly‐1+ B cells upon transfer of peritoneal cells into allotype‐congenic, newborn mice , 1987, European journal of immunology.