Toll-like receptor activity in recurrent aphthous ulceration.
BACKGROUND
Toll-like receptors (TLR) are membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal or host tissues. Activation of TLRs causes the production of cytokines that mediate inflammatory responses and drive T helper (Th) 1 and 2 cell development. As an exaggerated Th1 immune response is supposed to be involved in pathogenesis of Recurrent Aphthous Ulceration (RAU), we suggest that RAU patients may have an imbalance in TLR pathways.


METHODS
To study the function of TLR activation ex vivo, peripheral blood mononuclear cells (PBMCs) from RAU patients (n = 17) and controls (n = 17) were exposed to TLR2 [lipoteichoic acid (LTA), heat-killed Listeria monocytogenes (HKLM) and PamC3CSK4], TLR3 [Poly(I:C)], TLR4 [lipopolysaccharide (LPS)], TLR5 (flagellin) and TLR7 (imiquimod) ligands, and the time course of supernatant tumor necrosis factor-alpha (TNF-alpha) levels was quantified by enzyme-linked immunosorbent assay. In addition, serological and salivary TNF-alpha and soluble CD14 levels were quantified. The TNF-alpha produced by PBMCs in contact with each TLR ligand and autologous serum or saliva at the same time was also investigated. The data were analyzed by statistical multivariate tests.


RESULTS
The control group had a higher response to LTA, whereas RAU had a higher response to HKLM. LTA and LPS interfered with the salivary stimulation of the RAU PBMC and HKLM with the stimulation of the control. Autologous serum was capable of inhibiting TLR2 responsiveness to LTA and enhancing LPS stimulation. Salivary and serological levels of sCD14 and TNF-alpha were not significantly different.


CONCLUSIONS
Recurrent Aphthous Ulceration patients have an anomalous activity of the TLR2 pathway that probably influences the stimulation of an abnormal Th1 immune response.
Borra
Ricardo Carneiro
RC
Post-Graduation Program in Bio-Dentistry, Ibirapuera University (UNIB), São Paulo, Brazil. rcborra@gmail.com
de Mesquita Barros
Fabiana
F
de Andrade Lotufo
Mônica
M
Villanova
Fabiolla Elizabeth
FE
Andrade
Priscila Maria
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016014:Linear Models; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000276:immunology; D013281:Stomatitis, Aphthous / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D055815:Young Adult
D018950:Lipopolysaccharide Receptors; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha