Gene interactions and pathways from curated databases and text-mining
J Leukoc Biol 2001, PMID: 11358991

Peroxynitrite mediates cytokine-induced IL-8 gene expression and production by human leukocytes.

Zouki, C; József, L; Ouellet, S; Paquette, Y; Filep, J G

Recent studies indicate that nitric oxide (NO) or related compounds may regulate the production of interleukin (IL)-8, a potent proinflammatory chemokine. Here we report that peroxynitrite (ONOO(-)) formed by a reaction of NO with superoxide mediates IL-8 gene expression and IL-8 production in IL-1beta- and TNF-alpha-stimulated human leukocytes in whole blood. The NO synthase inhibitors aminoguanidine and N(G)-nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear (PMN) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90% in response to IL-1beta and TNF-alpha. Enhanced ONOO(-) formation was detected in granulocytes, monocytes, and lymphocytes after challenge with IL-1beta or TNF-alpha. The addition of ONOO(-) (0.2-80 microM) to whole blood increased nuclear accumulation of AP-1 and NF-kappaB in PMN and mononuclear leukocytes and augmented IL-8 mRNA expression and IL-8 production in a concentration-dependent fashion. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, attenuated approximately 70% of IL-8 release evoked by IL-1beta, TNF-alpha, or ONOO(-). These results indicate that ONOO(-) formation may underlie the action of cytokines towards IL-8 gene expression in human leukocytes.

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Text Mining Data

activator protein-1 (AP-1) ⊣ IL-8: " The NO synthase inhibitors aminoguanidine and N ( G ) -nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear ( PMN ) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90 % in response to IL-1beta and TNF-alpha "

IL-8 ⊣ TNF-alpha: " The NO synthase inhibitors aminoguanidine and N ( G ) -nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear ( PMN ) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90 % in response to IL-1beta and TNF-alpha "

IL-8 ⊣ IL-1beta: " The NO synthase inhibitors aminoguanidine and N ( G ) -nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear ( PMN ) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90 % in response to IL-1beta and TNF-alpha "

IL-8 ⊣ nuclear factor (NF)-kappaB: " The NO synthase inhibitors aminoguanidine and N ( G ) -nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear ( PMN ) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90 % in response to IL-1beta and TNF-alpha "

Manually curated Databases

No curated data.