Purchase this article with an account.
H. L. Rosenzweig, K. Galster, E. E. Vance, J. Ensign-Lewis, M. P. Davey, S. R. Planck, J. T. Rosenbaum; Nod2 Plays a Negative Regulatory Role in Ocular Inflammation Triggered by Peptidoglycan. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4836.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
NOD2 (nucleotide-binding oligomerization domain 2) plays a critical role in host defense and immunity. Its importance in regulation of ocular inflammation is underscored by the fact that mutations in NOD2 result in uveitis along with arthritis and dermatitis (called Blau syndrome). Intriguingly in the intestine where polymorphisms in NOD2 predispose to Crohn’s disease, Nod2 plays a protective role in inflammation triggered by the bacterial cell wall component, peptidoglycan (PGN). A ligand for NOD2, muramyl dipeptide (MDP) is derived from PGN. Whether Nod2 exerts a similar capacity in the regulation of ocular inflammation to microbial stimulants such as PGN has not been explored.
Mice deficient for Nod2, Nod1 or MyD88 and their wild-type (WT) controls were administered an intravitreal injection of PGN (a metabolite of which is the Nod2 agonist muramyl dipeptide), or Pam3CSK4 (a synthetic Toll-like receptor (TLR)-2 agonist). Ocular inflammation was assessed by intravital microscopy from 6 to 24 h following injection. Cytokine production was measured by ELISA at 5 h following injections.
PGN injection resulted in ocular inflammation that involved the TLR adaptor molecule MyD88. Similar to what was reported in bowel inflammation, Nod2 exerted a negative regulatory role because PGN-triggered eye inflammation was markedly exacerbated in the absence of Nod2. Cytokine production of IL-12p40 was increased in response to PGN injections and was further heightened by the absence of Nod2. Nod2 deficiency did not alter TNFα production triggered by PGN, suggesting a skewed inflammatory response occurs when Nod2 is absent. In contrast to Nod2, mice deficient in Nod1, responded to PGN comparably to WT mice, indicating a specific role for Nod2 in suppressing PGN-eye inflammation. Ocular inflammation induced by Pam3CSK4, which does not contain muramyl dipeptide, involved MyD88 but NOD2.
Our data support a newly identified role for Nod2 in the eye. Similar to what has been reported in colitis, Nod2 plays a protective role in suppressing ocular inflammation triggered by PGN.
This PDF is available to Subscribers Only