Pro-inflammatory role of NLRP3 inflammasome in experimental sterile corneal inflammation

Abstract

We evaluated the role of NLR family pyrin domain containing 3 (NLRP3) inflammasome in sterile corneal inflammation caused by lipopolysaccharide (LPS) or alkali burns in C57BL6 mice or NLRP3 KO ( Nlrp3 −/− ) mice. Various molecules related to the NLRP3 inflammasome were upregulated in C57BL6 mice after both alkali burn injury and LPS treatment. After alkali burn injury, the corneal opacity grade was significantly reduced in Nlrp3 −/− mice compared with C57BL6 mice. In Nlrp3 −/− mice, Gr-1 immunoreactivity and MMP-9 mRNA expression in the corneal stroma were significantly reduced by both LPS treatment and alkali burn injury. Quantitative PCR and immunohistochemistry revealed that IL-1β and MMP-9 expression in the corneal stroma were down-regulated in Nlrp3 −/− mice with both alkali burn injury and LPS treatment. These findings suggest that the NLRP3 inflammasome has a pro-inflammatory effect in the cornea by recruiting neutrophils to sites of inflammation.

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

“…Subsequently, NOD1, NOD2, NLRP1, NLRP3 were shown to be regulated during bacterial or fungal infections in humans [68][69][70] and mouse [71,72] cornea. However, several reports suggested the source of the NLR proteins to be derived from infiltrated neutrophils or monocytes at the site of infection [73][74][75]. In dry eye conditions, human patients with environment-induced dry eye [76], murine models of dry eye [77,78], and alkali-burned mice [79] all showed increased mRNA levels of NLRP3 in their conjunctival epithelium.…”

Subconjunctival Injection of Regulatory T Cells Potentiates Corneal Healing Via Orchestrating Inflammation and Tissue Repair After Acute Alkali Burn

“…After an acute corneal sterile injury, inflammatory cells exaggerated damages by releasing the influx of various deleterious cytokines and leukocytes. 15 As maintainers of immunological homeostasis, Tregs have been reported to recruit to corneas in virus-infected keratitis models. 16 Corroborating the findings of fluorescent activated cell sorting (FACS) analyses, Tregs infiltrated the local site of acute corneal alkali burn and continuously accumulated ( Fig.…”

Molecular Hydrogen Attenuated N-methyl-N-Nitrosourea Induced Corneal Endothelial Injury by Upregulating Anti-Apoptotic Pathway

“…In combination with the aptamer apoptosis-associated speck-like protein containing CARD (ASC), it mediates the activation of cysteine aspartate proteinase-1 (caspase-1) and the secretion of proinflammatory cytokines including IL-1β and IL-18. 21,51,[58][59][60][61][62][63][64] Activation signals can be provided by a variety of extracellular stimuli or molecules, including microbial toxins, as well as cellular damage events, such as mitochondrial dysfunction and ROS production. Among them, intracellular ROS and NLRP3 inflammasomes are mutually promoted.…”

“… 51 , 58 , 65 Studies have shown that both corneal and conjunctival epithelial cells harbor functional NLRP3 inflammasomes. 60 , 66 Due to the difference between infectious and noninfectious lesions, different corneal diseases may be associated with variation in expression of nucleotide binding and oligomerization domain-like receptor (NLR). 67 In our study, the immunofluorescence staining of ASC, caspase-1, and IL-1β of CECs were all enhanced under MNU, whereas they were weakened under H 2 , indicating that the function of NLRP3 inflammasomes could be activated by MNU and inhibited by H 2 .…”