NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes
Type 2 diabetes mellitus (T2DM), accounting for 90–95% cases of diabetes, is characterized by chronic inflammation. The mechanisms that control inflammation activation in T2DM are largely unexplored. Inflammasomes represent significant sensors mediating innate immune responses. The aim of this work...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/314 |
| _version_ | 1797415733548810240 |
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| author | Ilona M. Gora Anna Ciechanowska Piotr Ladyzynski |
| author_facet | Ilona M. Gora Anna Ciechanowska Piotr Ladyzynski |
| author_sort | Ilona M. Gora |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM), accounting for 90–95% cases of diabetes, is characterized by chronic inflammation. The mechanisms that control inflammation activation in T2DM are largely unexplored. Inflammasomes represent significant sensors mediating innate immune responses. The aim of this work is to present a review of links between the NLRP3 inflammasome, endothelial dysfunction, and T2DM. The NLRP3 inflammasome activates caspase-1, which leads to the maturation of pro-inflammatory cytokines interleukin 1β and interleukin 18. In this review, we characterize the structure and functions of NLRP3 inflammasome as well as the most important mechanisms and molecules engaged in its activation. We present evidence of the importance of the endothelial dysfunction as the first key step to activating the inflammasome, which suggests that suppressing the NLRP3 inflammasome could be a new approach in depletion hyperglycemic toxicity and in averting the onset of vascular complications in T2DM. We also demonstrate reports showing that the expression of a few microRNAs that are also known to be involved in either NLRP3 inflammasome activation or endothelial dysfunction is deregulated in T2DM. Collectively, this evidence suggests that T2DM is an inflammatory disease stimulated by pro-inflammatory cytokines. Finally, studies revealing the role of glucose concentration in the activation of NLRP3 inflammasome are analyzed. The more that is known about inflammasomes, the higher the chances to create new, effective therapies for patients suffering from inflammatory diseases. This may offer potential novel therapeutic perspectives in T2DM prevention and treatment. |
| first_indexed | 2024-03-09T05:53:48Z |
| format | Article |
| id | doaj.art-f1834a9944bc48d6b5fefeb96af4f2a0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:53:48Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f1834a9944bc48d6b5fefeb96af4f2a02023-12-03T12:15:51ZengMDPI AGCells2073-44092021-02-0110231410.3390/cells10020314NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 DiabetesIlona M. Gora0Anna Ciechanowska1Piotr Ladyzynski2Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, PolandNalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, PolandNalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4, 02-109 Warsaw, PolandType 2 diabetes mellitus (T2DM), accounting for 90–95% cases of diabetes, is characterized by chronic inflammation. The mechanisms that control inflammation activation in T2DM are largely unexplored. Inflammasomes represent significant sensors mediating innate immune responses. The aim of this work is to present a review of links between the NLRP3 inflammasome, endothelial dysfunction, and T2DM. The NLRP3 inflammasome activates caspase-1, which leads to the maturation of pro-inflammatory cytokines interleukin 1β and interleukin 18. In this review, we characterize the structure and functions of NLRP3 inflammasome as well as the most important mechanisms and molecules engaged in its activation. We present evidence of the importance of the endothelial dysfunction as the first key step to activating the inflammasome, which suggests that suppressing the NLRP3 inflammasome could be a new approach in depletion hyperglycemic toxicity and in averting the onset of vascular complications in T2DM. We also demonstrate reports showing that the expression of a few microRNAs that are also known to be involved in either NLRP3 inflammasome activation or endothelial dysfunction is deregulated in T2DM. Collectively, this evidence suggests that T2DM is an inflammatory disease stimulated by pro-inflammatory cytokines. Finally, studies revealing the role of glucose concentration in the activation of NLRP3 inflammasome are analyzed. The more that is known about inflammasomes, the higher the chances to create new, effective therapies for patients suffering from inflammatory diseases. This may offer potential novel therapeutic perspectives in T2DM prevention and treatment.https://www.mdpi.com/2073-4409/10/2/314NLRP3 inflammasomeinflammationtype 2 diabetes mellitusendothelial cells |
| spellingShingle | Ilona M. Gora Anna Ciechanowska Piotr Ladyzynski NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes Cells NLRP3 inflammasome inflammation type 2 diabetes mellitus endothelial cells |
| title | NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes |
| title_full | NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes |
| title_fullStr | NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes |
| title_full_unstemmed | NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes |
| title_short | NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes |
| title_sort | nlrp3 inflammasome at the interface of inflammation endothelial dysfunction and type 2 diabetes |
| topic | NLRP3 inflammasome inflammation type 2 diabetes mellitus endothelial cells |
| url | https://www.mdpi.com/2073-4409/10/2/314 |
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