Apoptotic cells induce NF-κB and inflammasome negative signaling.
As they undergo phagocytosis, most early apoptotic cells negatively regulate proinflammatory signaling and were suggested as a major mechanism in the resolution of inflammation. The dextran sulfate sodium model is generally viewed as an epithelial damage model suited to investigate innate immune res...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0122440&type=printable |
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| _version_ | 1849724176042033152 |
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| author | Amir Grau Adi Tabib Inna Grau Inna Reiner Dror Mevorach |
| author_facet | Amir Grau Adi Tabib Inna Grau Inna Reiner Dror Mevorach |
| author_sort | Amir Grau |
| collection | DOAJ |
| description | As they undergo phagocytosis, most early apoptotic cells negatively regulate proinflammatory signaling and were suggested as a major mechanism in the resolution of inflammation. The dextran sulfate sodium model is generally viewed as an epithelial damage model suited to investigate innate immune responses. Macrophages primed with LPS and subsequently exposed to DSS secrete high levels of IL-1β in an NLRP3-, ASC-, and caspase-1-dependent manner. The aim of this research was to test the therapeutic effect of a single dose of apoptotic cells in a DSS-colitis model and to explore possible mechanisms. Primary peritoneal macrophages, the DSS mice model, and Nlrp3-deficient mice, were used to assess the effect apoptotic cells on colitis. Immunohistochemistry, flow-cytometer, and western blots helped to explore the effect and mechanisms. Using a variety of NLRP3 triggering mechanisms, we show that apoptotic cells negatively regulate NF-κB and NLRP3 activation in primary peritoneal macrophages, at pre- and post-transcription levels, via inhibition of reactive oxygen species, lysosomal stabilization, and blocking K+ efflux. This property of apoptotic cells is demonstrated in a dramatic clinical, histological, and immunological amelioration of DSS colitis in Balb/c and B6 mice following a single administration of apoptotic cells. |
| format | Article |
| id | doaj-art-c2a7f67af8ea4054bd9b0c047c63be86 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c2a7f67af8ea4054bd9b0c047c63be862025-08-20T03:10:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012244010.1371/journal.pone.0122440Apoptotic cells induce NF-κB and inflammasome negative signaling.Amir GrauAdi TabibInna GrauInna ReinerDror MevorachAs they undergo phagocytosis, most early apoptotic cells negatively regulate proinflammatory signaling and were suggested as a major mechanism in the resolution of inflammation. The dextran sulfate sodium model is generally viewed as an epithelial damage model suited to investigate innate immune responses. Macrophages primed with LPS and subsequently exposed to DSS secrete high levels of IL-1β in an NLRP3-, ASC-, and caspase-1-dependent manner. The aim of this research was to test the therapeutic effect of a single dose of apoptotic cells in a DSS-colitis model and to explore possible mechanisms. Primary peritoneal macrophages, the DSS mice model, and Nlrp3-deficient mice, were used to assess the effect apoptotic cells on colitis. Immunohistochemistry, flow-cytometer, and western blots helped to explore the effect and mechanisms. Using a variety of NLRP3 triggering mechanisms, we show that apoptotic cells negatively regulate NF-κB and NLRP3 activation in primary peritoneal macrophages, at pre- and post-transcription levels, via inhibition of reactive oxygen species, lysosomal stabilization, and blocking K+ efflux. This property of apoptotic cells is demonstrated in a dramatic clinical, histological, and immunological amelioration of DSS colitis in Balb/c and B6 mice following a single administration of apoptotic cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0122440&type=printable |
| spellingShingle | Amir Grau Adi Tabib Inna Grau Inna Reiner Dror Mevorach Apoptotic cells induce NF-κB and inflammasome negative signaling. PLoS ONE |
| title | Apoptotic cells induce NF-κB and inflammasome negative signaling. |
| title_full | Apoptotic cells induce NF-κB and inflammasome negative signaling. |
| title_fullStr | Apoptotic cells induce NF-κB and inflammasome negative signaling. |
| title_full_unstemmed | Apoptotic cells induce NF-κB and inflammasome negative signaling. |
| title_short | Apoptotic cells induce NF-κB and inflammasome negative signaling. |
| title_sort | apoptotic cells induce nf κb and inflammasome negative signaling |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0122440&type=printable |
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