Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells

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40 Citations (Scopus)

Abstract

Toll-like receptor (TLR) family members are pattern-recognition receptors and very important molecules in innate immunity. Although TLRs are originally type I transmembrane receptors, soluble forms of TLRs are detected in human plasma and milk. This study showed that soluble TLR2 (sTLR2) is detected in human parotid saliva. Western blotting with anti-TLR2 antibodies (Abs) showed that three polypeptides are detected as sTLR2 with molecular weights of 55, 40 and 27 kDa, respectively. Parotid saliva neutralized the binding of anti-TLR2 polyclonal Ab to cell-surface TLR2 on THP-1, a human monocytic cell line. Immunohistochemical analysis revealed that TLR2 is expressed in serous and interlobular ductal cells of human salivary gland. Human salivary gland cell lines, AZA3 and HSY, constitutively expressed TLR2. Parotid saliva augmented IL-8 production of THP-1 cells stimulated with a synthetic TLR2 ligand, Pam3Cys-Ser-(Lys)4 (Pam3CSK4). Depletion of sCD14 from parotid saliva by immunoprecipitation eliminated the augmentation of IL-8 production, indicating that the augmentable effects depended on sCD14 in parotid saliva. On the other hand, preincubation of Pam3CSK4 with parotid saliva abrogated the augmentation of IL-8 production, indicating that sTLR2 in saliva bound to Pam3CSK4 and neutralized its function. These results suggest that parotid saliva modulates the TLR2-mediated immune responses with binary mechanisms via sTLR2 and sCD14 in the oral cavity.

Original languageEnglish
Pages (from-to)1969-1976
Number of pages8
JournalMolecular Immunology
Volume44
Issue number8
DOIs
Publication statusPublished - 2007 Mar

Keywords

  • Monocyte
  • Parotid saliva
  • Salivary gland
  • Soluble form
  • TLR2

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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