| First Author | Marinho Y | Year | 2020 |
| Journal | Biochim Biophys Acta Gen Subj | Volume | 1864 |
| Issue | 1 | Pages | 129461 |
| PubMed ID | 31676289 | Mgi Jnum | J:282487 |
| Mgi Id | MGI:6381027 | Doi | 10.1016/j.bbagen.2019.129461 |
| Citation | Marinho Y, et al. (2020) MSU Crystals induce sterile IL-1beta secretion via P2X7 receptor activation and HMGB1 release. Biochim Biophys Acta Gen Subj 1864(1):129461 |
| abstractText | BACKGROUD: The mechanism by which monosodium urate (MSU) crystals induce inflammation is not completely understood. Few studies have shown that MSU is capable of stimulating the release of IL-1beta in the absence of LPS treatment. The purinergic P2X7 receptor is involved in the release of IL-1beta in inflammatory settings caused by crystals, as is the case in silicosis. METHODS: We investigated the role of P2X7 receptor in sterile MSU-induced inflammation by evaluating peritonitis and paw edema. In in vitro models, we performed the experiments using peritoneal macrophages and THP-1 cells. We measured inflammatory parameters using ELISA and immunoblotting. We measured cell recruitment using cell phenotypic identification and hemocytometer counts. RESULTS: Our in vivo data showed that animals without P2X7 receptors generated less paw edema, less cell recruitment, and lower levels of IL-1beta release in a peritonitis model. In the in vitro model, we observed that MSU induced dye uptake by the P2X7 receptor. In the absence of the receptor, or when it was blocked, MSU crystals induced less IL-1beta release and this effect corresponded to the concentration of extracellular ATP. Moreover, MSU treatment induced HMGB1 release; pre-treatment with P2X7 antagonist reduced the amount of HMGB1 in cell supernatants. CONCLUSIONS: IL-1beta secretion induced by MSU depends on P2X7 receptor activation and involves HMGB1 release. GENERAL SIGNIFICANCE: We propose that cell activation caused by MSU crystals induces peritoneal macrophages and THP-1 cells to release ATP and HMGB1, causing IL-1beta secretion via P2X7 receptor activation. |
