TAILIEUCHUNG - Báo cáo khoa học: Glutamine and interleukin-1b interact at the level of Sp1 and nuclear factor-jB to regulate argininosuccinate synthetase gene expression

We previously demonstrated that the expression of the argininosuccinate synthetase (ASS) gene, a key step in nitric oxide production, is stimulated either by interleukin-1b[Brasse-Lagnel et al. (2005) Biochimie87, 403–9] or by glutamine in Caco-2 cells [Brasse-Lagnelet al. (2003) J. Biol. , 52504–10], through the activation of transcription factors nuclear factor-jB and Sp1, respectively. | ễFEBS Journal Glutamine and interleukin-1 b interact at the level of Sp1 and nuclear factor-KB to regulate argininosuccinate synthetase gene expression Carole Brasse-Lagnel Alain Lavoinne David Loeber Alain Fairand Christine Bole-Feysot Nicolas Deniel and Annie Husson Groupe AppareilDigestif Environnement et Nutrition Institut Federatif de Recherches Multidisciplinaires sur les Peptides Universite de Rouen France Keywords Caco-2 cells glutamine interleukin-1 b nuclear factor-KB Sp1 Correspondence Annie Husson ADEN EA 3234 IFR23 Faculte de Medecine-Pharmacie 22 boulevard Gambetta 76183 Rouen cedex France Fax 33 2 35 14 82 26 Tel 33 2 35 14 82 40 E-mail Received 11 June 2007 revised 10 August 2007 accepted 16 August 2007 doi We previously demonstrated that the expression of the argininosuccinate synthetase ASS gene a key step in nitric oxide production is stimulated either by interleukin-1 b 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-KB 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-1b 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-KB a interleukin-1 b inhibited the glutamine-stimulated DNA-binding of Sp1 which might be related to a decrease of its glutamine-induced O-glycosylation and b glutamine

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