Pattern recognition receptor‐mediated inflammation in diabetic vascular complications

Abstract

The innate immune system contains multiple classes of pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the intracellular and extracellular space. Although PRRs are indispensable for the detection and clearance of invading pathogens, dysregulated PRR activation by extrinsic and intrinsic factors leads to inflammatory diseases. PRRmediated inflammation has been shown to play a pivotal role in the pathogenesis of diabetic vascular complications (DVCs), which are the leading causes of morbidity and mortality in diabetic patients. Upon sensing hyperglycemiagenerated DAMPs, PRRs activate intracellular signaling pathways leading to the production of proinflammatory cytokines and chemokines in various cells of the kidney, brain, eye, and heart. The resulting chronic, low-grade inflammation contributes to DVCs. In this review, we summarize the role of PRRs in DVCs including diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. We propose that targeting PRRs and associated signaling pathways may be beneficial for the management of DVCs.

Protective mechanisms of Taiwanese green propolis toward high glucose‐induced inflammation via NLRP3 inflammasome signaling pathway in human gingival fibroblasts

“…Previous studies have shown that persistent levels of high glucose can enhance the generation of AGEs which may act as DAMPs to incite the NLRP3 in immune cells and other non-immune cell populations in the kidney, eye, heart, and nervous system which are diabetic complication-related organs, subsequently activating the downstream inflammatory cascades. 35 In line, our study the first time indicated that high glucose may induce NLRP3 inflammasomemediated caspase-1 activation and IL-1β cytokine production in the model of another non-immune cell population present in periodontium, namely HGFs, which is known as a body part affected by DM.…”

Advances in understanding the innate immune‐associated diabetic kidney disease

“…10,[26][27][28]44 Increased expression of NF-κB in renal tissues of humans and mice with diabetes and renal macrophages strongly correlated with the parameters of renal damage. [45][46][47][48][49] Phosphorylation of NF-κB p65 subunit in tubular and interstitial cells exacerbated inflammation and apoptosis, whereas the transgenic mice expressing the super-repressor IκBα in renal cells remained resistant to p65-mediated deleterious effect on kidney tissues. 50 The cytokine TNF-like weak inducer of apoptosis-dependent activation of noncanonical NF-κB pathway in tubular cells, as determined by the nuclear translocation of NF-κB RelB and p52 subunits, increased kidney injury.…”

Diabetic Oculomotor Nerve Palsy Displaying Enhancement of the Oculomotor Nerve in the Orbit and Cavernous Sinus on MRI

“…Among patients with ischemic ONP, our colleagues did not detect differences in the levels of some common plasmatic inflammatory factors such as erythrocyte sedimentation rate and C-reactive protein between patients with and those without the enhancement of the oculomotor nerve [8]. Two patients presented abnormal oligoclonal bands and intrathecal IgG synthesis, and it suggested that some other inflammatory components may accompany nerve enhancement in a hyperglycemia-independent manner [18, 19]. Breakdown of the blood-nerve barrier plays a pivotal pathophysiological role in diabetic neuropathy [20, 21].…”