Heparin-Binding EGF-Like Growth Factor Down Regulates Proinflammatory Cytokine-Induced Nitric Oxide and Inducible Nitric Oxide Synthase Production in Intestinal Epithelial Cells

Nitric Oxide ◽  
2002 ◽  
Vol 6 (2) ◽  
pp. 142-152 ◽  
Author(s):  
Maria L. Lara-Marquez ◽  
Veela Mehta ◽  
Marc P. Michalsky ◽  
James B. Fleming ◽  
Gail E. Besner
FEBS Journal ◽  
2004 ◽  
Vol 272 (2) ◽  
pp. 444-453 ◽  
Author(s):  
Martin Rumbo ◽  
Françoise Courjault-Gautier ◽  
Frédéric Sierro ◽  
Jean-Claude Sirard ◽  
Emanuela Felley-Bosco

2001 ◽  
Vol 281 (3) ◽  
pp. G688-G696 ◽  
Author(s):  
Osamu Kobayashi ◽  
Hiroto Miwa ◽  
Sumio Watanabe ◽  
Masahiko Tsujii ◽  
Raymond N. Dubois ◽  
...  

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression has been demonstrated in inflamed intestinal mucosa. Although regulation of COX-2 and iNOS expression has been studied extensively, the interplay between these two enzymes remains unclear. Because they play crucial roles in inflammation and/or carcinogenesis, we investigated whether COX-2 regulates iNOS expression and evaluated the effects of COX-2 inhibitor and arachidonic acid (AA) on iNOS induction. The COX-2 gene coding region was stably transfected into rat intestinal epithelial cells (RIE sense cells). After interferon-γ (IFN-γ) and lipopolysaccharide (LPS) administration, iNOS and COX-2 expression was evaluated by Western blotting. PGE2 was measured by the enzyme immunoassay (EIA) method. Expression of IFN response factor-1, phosphorylated extracellular signal-related kinase-1 and -2, and Iκ-Bα was evaluated. Activator protein-1 and nuclear factor-κB (NF-κB) were examined by gel mobility shift assay; a supershift assay was performed to identify the NF-κB complex components. JTE-522 or AA was added before IFN-γ and LPS administration, and effects on iNOS and PGE2 induction were evaluated by Western blotting or EIA. iNOS protein and mRNA expression was inhibited in RIE sense cells. Although NF-κB activation was suppressed and Iκ-Bα protein was more stable, respectively, in RIE sense cells, no difference was noted in other transcription factors. JTE-522 increased iNOS protein expression in RIE cells. We conclude that COX-2 suppressed iNOS expression in RIE cells through suppression of NF-κB by stabilizing Iκ-Bα.


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