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Synergistic Cytokine Production by ATP and $PGE_{2}$ via P2X4 and $EP_{3}$ Receptors in Mouse Bone-Marrow-Derived Mast Cells
| Content Provider | MDPI |
|---|---|
| Author | Obayashi, Kosuke Yoshida, Kazuki Ito, Masa-Aki Mori, Tetsuya Yamamoto, Kimiko Imai, Toshiyashu Matsuoka, Isao |
| Copyright Year | 2022 |
| Description | ATP is an important intercellular messenger in the extracellular space. In mast cells (MCs), ATP stimulates the ionotropic P2X4 receptor (P2X4R), resulting in enhanced degranulation and exacerbation of acute allergic reactions. In this study, we investigate whether ATP regulates inflammatory cytokine production in MCs. Gene expression was analyzed by quantitative RT-PCR, and cytokine production was measured using ELISA. The stimulation of mouse bone-marrow-derived MCs (BMMCs) with ATP alone had little effect on cytokine secretion. However, the co-stimulation with prostaglandin (PG) $E_{2}$ resulted in a marked increase in the secretion of various cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and IL-13, accompanied by an increase in their mRNA levels. The effects of ATP were inhibited by P2X4R antagonists and diminished in BMMCs derived from P2X4R-deficient mice, suggesting that P2X4R mediated the reaction. The effects of $PGE_{2}$ were mimicked by an $EP_{3}$ receptor $(EP_{3}$R) agonist and blocked by an $EP_{3}$R antagonist. The synergistic cytokine mRNA elevations induced by ATP and $PGE_{2}$ were blocked by nuclear factor-κB and $Ca^{2+}$-calcineurin signaling inhibitors. Altogether, these results suggest that combining P2X4R and $EP_{3}$R signaling enhances acute degranulation and the subsequent cytokine secretion, exacerbating allergic inflammation. |
| Starting Page | 616 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells11040616 |
| Journal | Cells |
| Issue Number | 4 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-02-10 |
| Access Restriction | Open |
| Subject Keyword | Cells Immunology Atp Bone-marrow-derived Mast Cells Prostaglandin E2 P2x4 Receptor Ep3 Receptor |
| Content Type | Text |
| Resource Type | Article |
