Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells
Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells
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DOI：
10.1016/j.molimm.2006.09.028
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Sugawara, Shunji
中科院分区：
文献类型：
--
作者：
Kuroishi, Toshinobu;Tanaka, Yukinori;Sugawara, Shunji
Toll样受体（TLR）家族成员是模式识别受体，是先天免疫中非常重要的分子。尽管TLR最初是I型跨膜受体，但在人血浆和乳汁中检测到可溶形式的TLR。这项研究表明，可溶性TLR 2（sTLR 2）在人腮腺唾液中检测。用抗TLR 2抗体（Abs）进行的Western blotting显示，三种多肽被检测为sTLR 2，分子量分别为55、40和27 kDa。腮腺唾液中和抗TLR 2多克隆抗体与THP-1（一种人单核细胞系）上细胞表面TLR 2的结合。免疫组化结果显示，TLR 2主要表达于人唾液腺的浆液性和小叶间导管细胞。人唾液腺细胞系AZA 3和HSY组成型表达TLR 2。腮腺唾液增加了用合成TLR 2配体Pam（3）Cys-Ser-（LyS）（4）（PaM 3CSK 4）刺激的THP-1细胞的IL-8产生。通过免疫沉淀消除腮腺唾液中的sCD 14消除了IL-8产生的增加，这表明可增加的作用依赖于腮腺唾液中的sCD 14。另一方面，将Pam（3）CSK（4）与腮腺唾液预孵育可消除IL-8产生的增加，表明唾液中的sTLR 2与PaM 3CSK 4结合并中和其功能。这些结果表明，腮腺唾液调节TLR 2介导的免疫反应，通过口腔中的sTLR 2和sCD 14的二元机制。(c)2006爱思唯尔有限公司版权所有。
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. Inummohistochemical 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, Pam(3)Cys-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 Pam(3)CSK(4) 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. (c) 2006 Elsevier Ltd. All rights reserved.