Palazzo Marco, Gariboldi Silvia, Zanobbio Laura, Dusio Giuseppina F, Selleri Silvia, Bedoni Marzia, Balsari Andrea, Rumio Cristiano
Department of Human Morphology, Pathology, Università degli Studi di Milano, 20133Milan, Italy.
Int Immunol. 2008 May;20(5):709-18. doi: 10.1093/intimm/dxn027. Epub 2008 Apr 7.
Toll-like receptors (TLRs) 4, 5, 7 and 9 belong to a family of proteins that recognize mainly conserved microbial motifs. Though each TLR has a highly specific ability to recognize a particular microbial pattern, recent papers suggest that some ligands are able to affect the expression of different TLRs. In this paper, we have investigated TLR4, 5, 7 and 9 expression, both at mRNA and protein level, following treatment of different intestinal epithelial cell lines with LPS, flagellin, loxiribine, CpG-oligodeoxynucleotide and peptidoglycan, to assess if the different TLR ligands may modulate the expression of the respective TLR and of the unrelated ones. Our results show that a cross-talk exists between TLRs and various ligands, indicating a cross-regulation among these pattern recognition receptors. In particular, TLR4 was generally down-regulated by treatment with ligands other than LPS, while flagellin and unrelated microbial-associated molecular patterns exerted a general stimulatory activity as regards TLR5 expression. Concerning TLR7 and 9, we have observed a more variable behaviour of the various cell lines with the different ligands. Together, our results demonstrate that the expression of TLRs in intestinal cells is highly dynamic and tightly regulated in response to encountered microbial stimuli.
Toll样受体（TLR）4、5、7和9属于一类主要识别保守微生物基序的蛋白质家族。尽管每种TLR识别特定微生物模式的能力具有高度特异性，但最近的论文表明，一些配体能够影响不同TLR的表达。在本文中，我们用脂多糖（LPS）、鞭毛蛋白、洛昔洛韦、CpG寡脱氧核苷酸和肽聚糖处理不同的肠上皮细胞系后，在mRNA和蛋白质水平上研究了TLR4、5、7和9的表达，以评估不同的TLR配体是否可能调节各自TLR以及不相关TLR的表达。我们的结果表明，TLR与各种配体之间存在相互作用，这表明这些模式识别受体之间存在交叉调节。特别是，除LPS外，用其他配体处理通常会使TLR4下调，而鞭毛蛋白和不相关的微生物相关分子模式对TLR5的表达具有普遍的刺激活性。关于TLR7和9，我们观察到不同细胞系对不同配体的反应更具变异性。总之，我们的结果表明，肠道细胞中TLR的表达具有高度动态性，并且在遇到微生物刺激时受到严格调控。
