The Roles of NLRP3 Inflammasome and ADAR1 in Diabetic Foot Ulcer

Abstract

Infected diabetic foot ulcer (DFU) is an important problem because it is a limb or even life threatening, and burdens a great financial load to the community. It’s shown that circulating inflammatory proteins are reputed to be of poor value for diagnosing DFU as lack of specificity. Therefore it's necessary to investigate newer discussed inflammatory parameters. NLRP3 inflammasome, a multiprotein complex consists of NLRP3, ASC and pro-caspase-1 and controls the production of IL-1β and IL-18, is an important contributor to the development of type 2 diabetes. The RNA-specific adenosine deaminase (ADAR1) is interferon-inducible double stranded (ds) RNA-binding protein, which is demonstrated to inhibit the production of type I interferons and various proinflammatory cytokines such as TNF-a and IL-6. But little is known about the ex vivo profile of NLRP3 inflammasome and ADAR1 in DFU. On this basis the aim of our study was to evaluate the role of NLRP3 inflammasome and ADAR1 in subjects with DFU in comparison with subjects without DFU. We completed a study including 20 healthy volunteers, 20 newly diagnosed type 2 diabetic (T2D) patients and 30 DFU patients (wagner2-4). Then peripheral blood mononuclear cells were collected from all subjects and NLRP3, ASC, Caspase-1, ADAR1 contents were detected by real-time PCR. The results showed that mRNA of NLRP3, ASC, Caspase-1 in T2D patients were significantly higher than those of healthy persons, while 2-fold lower than DFU patients (both P < 0.05); ADAR1 mRNA in T2D patients were significantly higher than those of healthy persons (P < 0.05). Interestingly, however, ADAR1 mRNA in DFU patients were decreased by 3-fold compared with T2D (P < 0.05), indicating that ADAR1 is increased in low-grade inflammation state but decreased in severe infectious state. This study suggests that NLRP3 inflammasome and ADAR1 may be useful markers to diagnose and follow the DFU. Further investigation is needed and it will be interesting to investigate the connection between them. Disclosure F. Wang: None. L. Zhao: None. W. Yang: None. H. He: None. Z. Mo: None.