Yolanda Cataño Cañizalez; Edith Uresti Rivera; Rocio Garcia Jacobo; Diana Portales Perez; Yadira Bastian; J Rodriguez Rivera; Roberto Gonzalez Amaro; Jose Enciso Moreno; Mariana Garcia Hernandez
Abstract
Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate ...
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Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients. Methods: AIM2 expression was analyzed by flow cytometry, it’s activity was assessed by measuring in vitro release of IL-1β induced by Poly (dA:dT), and mtDNA copy number was determined by quantitative real-time polymerase chain reaction. Results: Increased percent of AIM2+ cells were detected in monocytes from patients with T2D. Moreover, increased levels of IL-1β in monocytes cultures from T2D patients compared to healthy controls were observed. Also, association between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were detected. Likewise, the mtDNA copy number was augmented in T2D patients compared to control group. The mtDNA copies number was associated with body mass index (r=0.4231, P=0.0008) and TNF-α levels (r=0.5231, P=0.0005). In addition, increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1β were detected in a serum from T2D patients. Conclusion: These results suggest the involvement of AIM2 and mtDNA in the inflammatory process seen in T2D.
Mohammad Momeni; Mohammad Reza Mirzaei; Nahid Zainodini; Gholamhossein Hassanshahi; Mohammad Kazemi Arababadi
Volume 10, Issue 2 , June 2013, , Pages 103-109
Abstract
Background: Absent in Melanoma 2 (AIM2) is an intracellular microbial dsDNA sensor which plays an important role in production of proinflammatory cytokines through Apoptosis associated Speck-like protein containing a Caspase activation and recruitment domain (ASC) and Caspase-1. Micro-RNAs (miRNAs) play ...
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Background: Absent in Melanoma 2 (AIM2) is an intracellular microbial dsDNA sensor which plays an important role in production of proinflammatory cytokines through Apoptosis associated Speck-like protein containing a Caspase activation and recruitment domain (ASC) and Caspase-1. Micro-RNAs (miRNAs) play important roles in regulation of immune related genes. However, there is little information regarding the effects of miRNAs on the AIM2 and ASC expression. Objective: To determine the mRNA levels of AIM2 and ASC in Jurkat cell line following introducing miRNA-143 (MiR-143). Methods: MiR-143, a scrambled sequence and PBS were introduced separately, to the Jurkat cell lines and the mRNA levels of AIM2 and ASC were examined in parallel with beta-actin and GAPDH (as housekeeping genes) using Real-Time PCR technique. Results: The mRNA levels of AIM2 and ASC were significantly increased in the MiR-143 transfected Jurkat cells when compared to the scrambled sequence or PBS treated cells. Conclusions: MiR-143 can lead to increased expression of AIM2 and ASC mRNAs. Considering the significance of AIM2 and ASC in DNA sensing and inflammosome formation, it can be considered as a therapeutic agent for the treatment of chronic infectious diseases, especially viral infections.