Mitochondrial DNA leakage exacerbates odontoblast inflammation through gasdermin D-mediated pyroptosis.
Mitochondrial DNA leakage exacerbates odontoblast inflammation through gasdermin D-mediated pyroptosis.
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线粒体DNA泄漏通过gasdermin D介导的细胞焦亡加剧成牙本质细胞炎症
DOI：
10.1038/s41420-021-00770-z
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发表时间：
2021-12-09
影响因子：
7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zhang YF;Zhou L;Mao HQ;Yang FH;Chen Z;Zhang L
Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship.
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影响因子：
8.7
作者：
Man SM;Karki R;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
4
作者：
Farges JC;Alliot-Licht B;Baudouin C;Msika P;Bleicher F;Carrouel F
通讯作者：
Carrouel F
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Li, Yinyin;Shen, Yi;Weyand, Cornelia M.
通讯作者：
Weyand, Cornelia M.