Glutamine and interleukin-1β interact at the level of Sp1 and nuclear factor-κB to regulate argininosuccinate synthetase gene expression
| Autor: | Annie Husson, David Loeber, Christine Bole-Feysot, Nicolas Deniel, Alain Fairand, Alain Lavoinne, Carole Brasse-Lagnel |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
chemistry.chemical_classification
Regulation of gene expression biology medicine.medical_treatment Argininosuccinate synthase Cell Biology Metabolism Biochemistry Molecular biology Amino acid Glutamine Cytokine chemistry Gene expression biology.protein medicine Molecular Biology Transcription factor |
| Zdroj: | FEBS Journal. 274:5250-5262 |
| ISSN: | 1742-464X |
| DOI: | 10.1111/j.1742-4658.2007.06047.x |
| Popis: | We previously demonstrated that the expression of the argininosuccinate synthetase (ASS) gene, a key step in nitric oxide production, is stimulated either by interleukin-1beta[Brasse-Lagnel et al. (2005) Biochimie 87, 403-9] or by glutamine in Caco-2 cells [Brasse-Lagnel et al. (2003) J. Biol. Chem. 278, 52504-10], through the activation of transcription factors nuclear factor-kappaB and Sp1, respectively. In these cells, the fact that glutamine stimulated the expression of a gene induced by pro-inflammatory factors appeared paradoxical as the amino acid is known to exert anti-inflammatory properties in intestinal cells. We therefore investigated the effect of simultaneous addition of both glutamine and interleukin-1beta on ASS gene expression in Caco-2 cells. In the presence of both compounds for 4 h, the increases in ASS activity, protein amount and mRNA level were almost totally inhibited, implying a reciprocal inhibition between the amino acid and the cytokine. The inhibition was exerted at the level of the transcription factors Sp1 and nuclear-kappaB: (a) interleukin-1beta inhibited the glutamine-stimulated DNA-binding of Sp1, which might be related to a decrease of its glutamine-induced O-glycosylation, and (b) glutamine induced per se a decrease in the amount of nuclear p65 protein without affecting the stimulating effect of interleukin-1beta on nuclear factor-kappaB, which might be related to the metabolism of glutamine into glutamate. The present results constitute the first demonstration of a reciprocal inhibition between the effects of an amino acid and a cytokine on gene expression, and provide a molecular basis for the protective role of glutamine against inflammation in the intestine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|