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-gamma) 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-gamma induced a marked NO production in TH2.52 cells through the expression of an inducible type of NO synthase (iNOS). IFN-gamma-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-gamma. 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-gamma-induced cell death. Therefore, IFN-gamma-induced NO production was possible in causing cell death in TH2.52 cells. Further, IFN-gamma-induced NO production and cell death significantly were prevented by interleukin-4, a representative Th2 cytokine. The immunological significance of IFN-gamma-induced NO production in a mouse B1-like cell line is discussed.
Koide
Naoki
N
Department of Microbiology and Immunology, and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University Aichi 480-1195, Nagakute, Japan.
Sugiyama
Tsuyoshi
T
Mu
Mya Mya
MM
Mori
Isamu
I
Yoshida
Tomoaki
T
Hamano
Teruaki
T
Yokochi
Takashi
T
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018956:CD5 Antigens / Q000032:analysis*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D053613:Janus Kinase 1; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
D017304:Annexin A5; D018956:CD5 Antigens; D004791:Enzyme Inhibitors; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases