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(Investigative Ophthalmology and Visual Science. 2007;48:1711-1717.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0807
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Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis

John H. Chang,1,2 Taline Hampartzoumian,1 Beth Everett,1 Andrew Lloyd,1 Peter J. McCluskey,1,2 and Denis Wakefield1,2

1From the Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; and the 2Department of Ophthalmology, St. Vincent’s Hospital, Sydney, NSW, Australia.

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-{gamma} 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-1ß 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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H. Mashimo, N. Ohguro, S. Nomura, N. Hashida, K. Nakai, and Y. Tano
Neutrophil Chemotaxis and Local Expression of Interleukin-10 in the Tolerance of Endotoxin-Induced Uveitis
Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5450 - 5457.
[Abstract] [Full Text] [PDF]


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