The NALP3/Cryopyrin-Inflammasome Complex is Expressed in LPS-Induced Ocular Inflammation

Abstract

In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase-1 which induces IL-1β. In murine LPS-induced ocular inflammation, the production of IL-1β is increased. We suggest that NALP3- or NALP1-inflammasome complex can be participating in the LPS-induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase-1, IL-1β, and IL-18 was determined. Infiltrated leukocytes producing IL-1β in the anterior chamber were found at 12-hour posttreatment. A high upregulated expression of NALP3, ASC, caspase-1, IL-1β, and IL-18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3-, but not NALP1-inflammosome complex, is participating in the murine LPS-induced ocular inflammation.

The NLRP3 inflammasome is active but not essential in endotoxin-induced uveitis

“…Despite the concurrence of uveitis with systemic autoinflammatory disorders involving IL-1 β , little is understood regarding the inflammasome pathway in intraocular inflammation. The messenger RNA (mRNA) transcripts of inflammasome components (NLRP3, ASC, and caspase-1) are known to be present in murine eye tissues [14], indicating their potential involvement in uveitis, yet their functional contribution remains to be determined. The eye’s susceptibility to intraocular injection of LPS and the ensuing uveitis in mice have been well documented by our group and others.…”

NLRs in immune privileged sites

“…This suggests unique expression profiles of NLRs within immune-privileged sites and that that species differences may be observed as well. Few studies have investigated the extent to which NLRs may be differentially regulated in eye tissue; albeit reports of NOD1, NOD2, NLRP3 expression in murine eye tissue [19–22] and human vascular endothelial cells from iris, choroid and retina express NOD2 [23] have been published. In general, studies to corroborate mRNA expression profiles at the protein level and to further distinguish cellular localization of NLRs within the CNS or eye are lacking.…”

“…NLRP3 is constitutively expressed at the mRNA level in murine eyes and is upregulated as a consequence of systemic LPS exposure [37]. Our own studies have confirmed expression of NLRP3 protein in murine eyes and have investigated its function in an established acute uveitis model, historically referred to as endotoxin-induced uveitis [38].…”

Molecular Signaling and Ocular Inflammation: An Update on the NOD-Like Receptors (NLRs)

“…NLRP3 may be involved in ocular Behçet's in human patients [28,29], but little is known about its functional role in experimental models of uveitis. Constitutive expression of NLRP3 occurs at the transcriptional and translational level in healthy murine ocular tissue and is upregulated as a consequence of LPS exposure [30,31]. Studies have investigated its function in an established acute uveitis model adapted in mice, historically referred to as endotoxininduced uveitis (EIU) [32].…”