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
; 48(4): 1711-7, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17389503
ABSTRACT
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-1beta 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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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Monócitos
/
Uveíte Anterior
/
Receptor 2 Toll-Like
/
Receptor 4 Toll-Like
/
Neutrófilos
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália