Saturated fatty acids were proposed to activate the NLRP3 inflammasome, a molecular platform that mediates the processing of interleukin (IL)-1β and IL-18. However, the mechanisms underlying the miRNA-mediated regulation of palmitate (PA)-induced inflammasome activation are unclear. We examined the role of miR-132 in PA-induced NLRP3 inflammasome activation in THP-1 cells. To understand the regulatory role of miR-132 in inflammasome activation, we either overexpressed or suppressed miR-132 in THP-1 cells that expressed the NLRP3 inflammasome in response to stimulation by PA. We analyzed the mRNA and protein levels of NLRP3, caspase-1 p10, IL-18, and IL-1β; caspase-1 activity; and IL-1β secretion. The presence of PA activated the NLRP3 inflammasome and increased miR-132 expression. Overexpression of miR-132 reduced caspase-1 p10, IL-18, and IL-1β, while the suppression of miR-132 enhanced inflammasome activation. In addition, miR-132 regulated the mRNA and protein expression of FOXO3, which is a potential target of miR-132 in these cells. FOXO3 suppression by small interfering RNA decreased NLRP3 inflammasome activity stimulated by PA. Knockdown of FOXO3 attenuated NLRP3 inflammasome activation by the miR-132 inhibitor. Based on these findings, we conclude that miR-132 negatively regulates PA-induced NLRP3 inflammasome activation through FOXO3 down-regulation in THP-1 cells.

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Purpose: Anti-vascular endothelial growth factor (anti-VEGF) agents are good therapeutic options for diabetic macular edema (DME), especially in patients with DME that is refractory or shows delayed response to anti-VEGF treatment. We investigated the change of proteinuria following intravitreal bevacizumab injection (IVB) as a potential biomarker for treatment-responsiveness in patients with DME. Methods: This pilot study was performed as secondary analysis of patients with diabetic retinopathy (DR) from prospectively enrolled patients scheduled for IVB from May 2018 to December 2018. Fifty-three patients with DR (30 with DME and 23 without DME) were initially included, and 46 eyes were finally included for analysis after propensity score matching. Urine tests were performed within 1 month before and 7 ± 1 days after IVB. The concentrations of urine protein and albumin were quantitatively measured, and the urinary albumin-to-creatinine ratio (UACR) was calculated from data before and after IVB. Results: There were no significant differences in mean concentrations of urine albumin and protein between patients with and without DME. More patients in the DME group showed abnormal level of albuminuria both before and after IVB, but these differences were not statistically significant between the groups. A correlation analysis revealed no significant association between change in UACR and that of central retinal thickness. Conclusion: Change in proteinuria was not a proper biomarker of the response to IVB in patients with DME.

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