Limits...
Activation of the NF κ B Pathway Enhances AhR Expression in Intestinal Caco-2 Cells.

Champion S, Sauzet C, Bremond P, Benbrahim K, Abraldes J, Seree E, Barra Y, Villard PH - ISRN Toxicol (2013)

Bottom Line: This was associated with an increase in AhR promoter activity.Similar results were obtained with conditioned media from PMA-treated THP-1 cells.Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

View Article: PubMed Central - PubMed

Affiliation: IMBE-UMR CNRS 7263, IRD 237 Aix-Marseille Université Campus Timone, Faculté de Pharmacie, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.

ABSTRACT
Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 β enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF κ B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 β blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

No MeSH data available.


Related in: MedlinePlus

Effect of 100 nM PMA on AhR promoter activity after sequential mutation of the 3 putative NFκB binding sites. *: P < 0.05 versus untreated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3818893&req=5

fig3: Effect of 100 nM PMA on AhR promoter activity after sequential mutation of the 3 putative NFκB binding sites. *: P < 0.05 versus untreated cells.

Mentions: To see whether AhR induction (mRNA) in response to PMA was associated with an increase in AhR transcription, reporter gene expression was analyzed using the p3.48 construct in which luciferase expression was driven by the AhR promoter. Treating WT p3.48-transfected Caco-2 cells with 100 nM PMA led to a 2.3-fold increase in luciferase expression (Figure 3), showing that increased AhR expression in response to PMA was mainly of transcriptional origin.


Activation of the NF κ B Pathway Enhances AhR Expression in Intestinal Caco-2 Cells.

Champion S, Sauzet C, Bremond P, Benbrahim K, Abraldes J, Seree E, Barra Y, Villard PH - ISRN Toxicol (2013)

Effect of 100 nM PMA on AhR promoter activity after sequential mutation of the 3 putative NFκB binding sites. *: P < 0.05 versus untreated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818893&req=5

fig3: Effect of 100 nM PMA on AhR promoter activity after sequential mutation of the 3 putative NFκB binding sites. *: P < 0.05 versus untreated cells.
Mentions: To see whether AhR induction (mRNA) in response to PMA was associated with an increase in AhR transcription, reporter gene expression was analyzed using the p3.48 construct in which luciferase expression was driven by the AhR promoter. Treating WT p3.48-transfected Caco-2 cells with 100 nM PMA led to a 2.3-fold increase in luciferase expression (Figure 3), showing that increased AhR expression in response to PMA was mainly of transcriptional origin.

Bottom Line: This was associated with an increase in AhR promoter activity.Similar results were obtained with conditioned media from PMA-treated THP-1 cells.Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

View Article: PubMed Central - PubMed

Affiliation: IMBE-UMR CNRS 7263, IRD 237 Aix-Marseille Université Campus Timone, Faculté de Pharmacie, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.

ABSTRACT
Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 β enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF κ B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 β blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

No MeSH data available.


Related in: MedlinePlus