Gamma Interferon-Induced Nitric Oxide Production in Mouse CD5 super(+) 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 super(+) 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 BI 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.