Genotype-specific regulation of oral innate immunity by T2R38 taste receptor.
Genotype-specific regulation of oral innate immunity by T2R38 taste receptor.
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DOI：
10.1016/j.molimm.2015.10.012
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Chung WO
中科院分区：
文献类型：
--
作者：
Gil S;Coldwell S;Drury JL;Arroyo F;Phi T;Saadat S;Kwong D;Chung WO
苦味受体T2R38已被证明调节上呼吸道上皮粘膜的先天免疫反应。此外，T2R38中的SNP影响对6-丙基硫氧嘧啶(PROP)的敏感性，并与龋病风险/预防相关。然而，关于T2R38在口腔细菌先天免疫反应中作用的研究尚未见报道。我们假设T2R38调节口服先天免疫，并且这种调节是基因特异性的。原代携带PAV/PAV、AVI/PAV和AVI/AVI三种常见基因的牙龈上皮细胞分别用致龋菌变形链球菌、牙周病原菌牙龈卟啉单胞菌和非病原菌核梭杆菌刺激。定量逆转录聚合酶链式反应分析T2R38mRNA，用T2R38特异性小干扰RNA和酶联免疫吸附试验检测不同供体细胞对hBD-2、IL-1α和IL-8的诱导。实验一式两份，重复三次。变形链球菌对T2R38mRNA的诱导在PAV/PAV中最高(是未刺激对照组的4.3倍；p&t；0.05)，而在AVI/AVI中最低(1.2倍)。在PAV/PAV中，当T2R38被沉默时，HBD-2对变形链球菌的分泌减少了77%。经变形链球菌刺激后，PAV/PAV组IL-1α的分泌明显高于AVI/PAV组和AVI/AVI组，而抑制T2R38后IL-1 DNA的分泌减少了一半(P<0.05)。AVI/AVI组的T2R38表达增加4.4倍(P<0.05)，而PAV/PAV组和AVI/PAV组的表达水平与对照组接近。当T2R38被沉默时，AVI/AVI的IL-1α和IL-8的分泌水平下降，而PAV/PAV的变化不明显。我们的数据表明，T2R38对牙龈先天免疫的调节依赖于基因，PAV/PAV携带者诱导高水平HBD-2的能力可能是这一组预防龋病的一个原因。
The bitter taste receptor T2R38 has been shown to regulate mucosal innate immune responses in the upper airway epithelium. Furthermore, SNPs in T2R38 influence the sensitivity to 6-n-propylthiouracil (PROP) and are associated with caries risk/protection. However, no study has been reported on the role of T2R38 in the innate immune responses to oral bacteria. We hypothesize that T2R38 regulates oral innate immunity and that this regulation is genotype-specific. Primary gingival epithelial cells carrying three common genotypes, PAV/PAV (PROP super-taster), AVI/PAV (intermediate) and AVI/AVI (non-taster) were stimulated with cariogenic bacteria Streptococcus mutans, periodontal pathogen Porphyromonas gingivalis or non-pathogen Fusobacterium nucleatum. QRT-PCR analyzed T2R38 mRNA, and T2R38-specific siRNA and ELISA were utilized to evaluate induction of hBD-2 (antimicrobial peptide), IL-1α and IL-8 in various donor-lines. Experiments were set up in duplicate and repeated three times. T2R38 mRNA induction in response to S. mutans was highest in PAV/PAV (4.3-fold above the unstimulated controls; p<0.05), while lowest in AVI/AVI (1.2-fold). In PAV/PAV, hBD-2 secretion in response to S. mutans was decreased by 77% when T2R38 was silenced. IL-1α secretion was higher in PAV/PAV compared to AVI/PAV or AVI/AVI with S. mutans stimulation, but it was reduced by half when T2R38 was silenced (p<0.05). In response to P. gingivalis, AVI/AVI showed 4.4-fold increase (p<0.05) in T2R38 expression, whereas the levels in PAV/PAV and AVI/PAV remained close to that of the controls. Secretion levels of IL-1α and IL-8 decreased in AVI/AVI in response to P. gingivalis when T2R38 was silenced (p<0.05), while the changes were not significant in PAV/PAV. Our data suggest that the regulation of gingival innate immunity by T2R38 is genotype-dependent and that the ability to induce a high level of hBD-2 by PAV/PAV carriers may be a reason for protection against caries in this group.