IL-8→Tumor Necrosis Factor-alpha→Nitric Oxide→STAT1

• 19259778(IL-8): Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-alpha and IL-8 production by human peripheral blood mononuclear cells.

  LPS increased IL-8 concentration (2361 + / - 385 pg/ml) , but paricalcitol returned it to its basal level (1849 + / - 417 pg/ml).

• 15157897(Tumor Necrosis Factor-alpha): Differential regulation of cytokine and chemokine production in lipopolysaccharide-induced tolerance and priming.

  LPS induced IL-8 production and to a lesser extent IL-1beta and GMCSF.

• 17622798(Nitric Oxide): LPS/IFNgamma-induced RAW 264.7 apoptosis is regulated by both nitric oxide-dependent and -independent pathways involving JNK and the Bcl-2 family.

  Lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) stimulate macrophages to produce nitric oxide (NO) via inducible nitric oxide synthase (iNOS) and activate stress signaling cascades including the c-jun-N-terminal kinase (JNK) pathway.

• 20381453(STAT1): IFNgamma mediates DUOX2 expression via a STAT-independent signaling pathway.

  These data provide insights into a novel IFNgamma signaling pathway with potential importance for regulation of host defense responses.