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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 proteasome inhibitor cocktail on 100 nM PMA-mediated AhR and IL-1β transcript induction. C: control Caco-2 cells; PMA: 100 nM PM-treated Caco-2 cells; C-IP: control Caco-2 cells pretreated with proteasome inhibitor cocktail; PMA-IP: Caco-2 cells pretreated with proteasome inhibitor cocktail and treated with 100 nM PMA. *: P < 0.05 versus control.
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fig4: Effect of proteasome inhibitor cocktail on 100 nM PMA-mediated AhR and IL-1β transcript induction. C: control Caco-2 cells; PMA: 100 nM PM-treated Caco-2 cells; C-IP: control Caco-2 cells pretreated with proteasome inhibitor cocktail; PMA-IP: Caco-2 cells pretreated with proteasome inhibitor cocktail and treated with 100 nM PMA. *: P < 0.05 versus control.

Mentions: In order to gain stronger confirmation of the role of NFκB in AhR expression, we reduced NFκB activation by inhibiting IκB degradation using a supplier-specified proteasome inhibitors cocktail that includes proteasome inhibitor I, lactacystin, and MG-132. As shown in Figure 4, using the proteasome inhibitor cocktail led to a 65% reduction in AhR induction by 100 nM PMA, along with an 86% decrease in IL-1β enhancement, demonstrating that the proteasome inhibitor cocktail was able to prevent the IL-1β induction triggered by the NFκB transduction pathway.


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 proteasome inhibitor cocktail on 100 nM PMA-mediated AhR and IL-1β transcript induction. C: control Caco-2 cells; PMA: 100 nM PM-treated Caco-2 cells; C-IP: control Caco-2 cells pretreated with proteasome inhibitor cocktail; PMA-IP: Caco-2 cells pretreated with proteasome inhibitor cocktail and treated with 100 nM PMA. *: P < 0.05 versus control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3818893&req=5

fig4: Effect of proteasome inhibitor cocktail on 100 nM PMA-mediated AhR and IL-1β transcript induction. C: control Caco-2 cells; PMA: 100 nM PM-treated Caco-2 cells; C-IP: control Caco-2 cells pretreated with proteasome inhibitor cocktail; PMA-IP: Caco-2 cells pretreated with proteasome inhibitor cocktail and treated with 100 nM PMA. *: P < 0.05 versus control.
Mentions: In order to gain stronger confirmation of the role of NFκB in AhR expression, we reduced NFκB activation by inhibiting IκB degradation using a supplier-specified proteasome inhibitors cocktail that includes proteasome inhibitor I, lactacystin, and MG-132. As shown in Figure 4, using the proteasome inhibitor cocktail led to a 65% reduction in AhR induction by 100 nM PMA, along with an 86% decrease in IL-1β enhancement, demonstrating that the proteasome inhibitor cocktail was able to prevent the IL-1β induction triggered by the NFκB transduction pathway.

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