Details

Autor(en) / Beteiligte

• Salem, Mabrouka
• Tremblay, Alain
• Pelletier, Julie
• Robaye, Bernard
• Sévigny, Jean

Titel

P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells

Ist Teil von

• Frontiers in pharmacology, 2018-02, Vol.9, p.149-149

Ort / Verlag

Frontiers Media S.A

Erscheinungsjahr

2018

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y 6 receptors. qRT-PCR experiments showed that P2Y 6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y 6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y 6 ( P2ry6 -/- ). Similar expression levels of P2Y 1 , P2Y 2 , P2X2, P2X4, and A 2A were detected in P2ry6 -/- and WT IEC. Agonists of TLR3 (poly(I:C)), TLR4 (LPS), P2Y 1 , and P2Y 2 increased the expression and secretion of CXCL10 more prominently in P2ry6 -/- IEC than in WT IEC. CXCL10 expression and secretion induced by poly(I:C) in both P2ry6 -/- and WT IEC were inhibited by general P2 antagonists (suramin and Reactive-Blue-2), by apyrase, and by specific antagonists of P2Y 1 , P2Y 2 , P2Y 6 (only in WT), and P2X4. Neither adenosine nor an A 2A antagonist had an effect on CXCL10 expression and secretion. Macrophage chemotaxis was induced by the supernatant of poly(I:C)-treated IEC which was consistent with the level of CXCL10 secreted. Finally, the non-nucleotide agonist FGF2 induced MMP9 mRNA expression also at a higher level in P2ry6 -/- IEC than in WT IEC. In conclusion, extracellular nucleotides regulate CXCL10 expression and secretion by IEC. In the absence of P2Y 6 , these effects are modulated by other P2 receptors also present on IEC. These data suggest that the presence of P2Y 6 regulates chemokine secretion and may also regulate IEC homeostasis.