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John H. Chang, Taline Hampartzoumian, Beth Everett, Andrew Lloyd, Peter J. McCluskey, Denis Wakefield; Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(4):1711-1717. doi: 10.1167/iovs.06-0807.
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purpose. To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU).
methods. Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16+ neutrophils and CD14+ monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR.
results. A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-γ production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1β in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation.
conclusions. There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU.
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