The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription.

摘要: Inducible nitric oxide synthase (iNOS) metabolizes L-arginine to produce (NO) which was originally identified in myeloid cells as a host defense mechanism against pathogens. Recent studies, however, have revealed that iNOS is often induced tumor and the microenvironment. Compelling experimental data shown promotes development certain cellular context suppresses other conditions. The molecular mechanisms underlying these contrasting functions of unknown. Because by inflammatory signals, it therefore likely could be controlled signaling pathways, remains determined. expressed colon carcinoma Colon cell lines were used elucidate expression. Chromatin immunoprecipitation electrophoretic mobility shift assay determine IFNγ-activated pSTAT1 NF-κB association with chromatin DNA nos2 promoter. We show here dramatically up-regulated inflammed human tissues compared normal tissue. either or immune within On level, proinflammatory IFNγ signals induce expression cancer cells. further demonstrate directly binds NOS2 promoter regulate Although neither pathway nor alone sufficient cells, synergistically Furthermore, we up-regulates IRF8 augment induction More interestingly, observed p65/p65 p50/p50 homodimers, not canonical p65/p50 heterodimer, IFNγ-induced acts concert both In complexes bind are homodimers.