N as Islet-Brain1 (IB1) protein or c-Jun N-terminal kinase (JNK) interacting protein-1 (JIP1)) is usually a scaffold protein that is hugely expressed inside the brain [25] and pancreatic -cells [26]. There is certainly accumulating proof that MAPK8IP1 plays an essential function in -cell survival and function. Even though MAPK8IP1 has been identified as a potential candidate gene for T2D [27], other studies have demonstrated that the loss of MAPK8IP1 function didn’t contribute for the development of diabetes [28,29]. Lately, we demonstrated that MAPK8IP1 expression is lowered in human diabetic islets and that the silencing of Mapk8ip1 in INS-1 cells impaired insulin secretion and lowered glucose uptake levels [30]. Furthermore, MAPK8IP1 has been reported to mediate the JNK signaling pathway [31], plus the latter was implicated in inflammasome activation [32,33]. To our knowledge, no studies have investigated the function of MAPK8IP1 in pancreatic cell inflammasome regulation. Therefore, within this study, we aimed to explore the functional part of MAPK8IP1 in -cell inflammasomes activation/regulation and its impact on -cell survival and function. 2. Final results 2.1. Expression Profiles of Pro-Inflammatory and Inflammasome-Related Genes (IRGs) in Human Pancreatic Islets Herein, we investigated the expression of a number of IRGs making use of published RNA-seq and qPCR expression analyses of human pancreatic islets. As is shown in Figure 1A, an RNA-seq expression analysis of 26 IRG genes showed that IL-6, NF-1, MAPK8IP1, and pannexin1 (PANX1) were among one of the most very expressed genes in the human islets, whereas NLR family members pyrin domain containing 12 (NLRP12), NLR family pyrin domain containing 9 (NLRP9), absent in melanoma 2 (AIM2), NLRP3, and NLRC4 have been amongst the lowest expressed genes. For further confirmation, we evaluated the expression of 11 key genes involved in inflammasome activation in healthy human islets obtained from non-diabetic donors by qPCR. Determined by Ct values, an mRNA expression evaluation revealed that NF-1, ASC, and IL-18 have been among the more hugely expressed genes in human islets, when AIM2 and NLRC4 had been amongst those together with the lowest expression (Figure 1B). Subsequent, we correlated the expression of MAPK8IP1 with IRGs within the pancreatic islets.X-alpha-Gal As illustrated in Figure 1C , the expression of MAPK8IP1 correlated positively (p 0.Andecaliximab 05) with that of NLRP3, GSDMD, and ASC (also known as PYCARD), whereas it correlated inversely with that of IL-18, IL-1, IL-6, CARD17+CASP1, and NF-1.PMID:24360118 (Figure 1F ). Alternatively, AIM2, NLRP9, and NLRC4 showed no expressionInt. J. Mol. Sci. 2023, 24,three ofInt. J. Mol. Sci. 2023, 24,three of 18 that of NLRP3, GSDMD, and ASC (also referred to as PYCARD), whereas it correlated inversely with that of IL-18, IL-1, IL-6, CARD17+CASP1, and NF-1. (Figure 1F ). On the other hand, AIM2, NLRP9, and NLRC4 showed no expression correlation with MAPK8IP1 (Figure 1K ). Collectively, these Together, these outcomes reveal MAPK8IP1 is correcorrelation with MAPK8IP1 (Figure 1K ). outcomes reveal that the expression ofthat the expression lated with essential IRGs in human islets.of MAPK8IP1 is correlated with important IRGs in human islets.Figure 1. Expression profiles of IRGs in human pancreatic islets. (A) RNA-seq expression of NLRP12, NLRP9, AIM2, NLRP3, NLRC4, CASP12, NLRP1, BCL2, PYCARD, NR4A3, MAPK11, NLRC5, MAP3K8, GSDMD, GSDMB, CARD6, IL-1, CARD17+CASP1, SOCS3, NR4A1, TRAF6, IL-18, PANX1, MAPK8IP1, NF-1, and IL-6 in non-diabetic human islets (n = 51) obtained from publicly readily available datase.
