Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain.
J Physiol Biochem. 2022 Aug;78(3):689-701. doi: 10.1007/s13105-022-00897-2. Epub 2022 Jun 7.
Intestinal serotonergic system is a key modulator of intestinal homeostasis; however, its regulation is still unclear. Toll-like receptor 9 (TLR9), an innate immune receptor, detects different external agents in the intestine, preserving intestinal integrity. Since little is known about TLR9 role in the intestine, our aim was to address the potential regulation between TLR9 and intestinal serotonergic system. Caco-2/TC7 cell line and intestinal tract of Tlr9 mice were used in this study. Serotonin uptake studies were performed, and molecular expression of different serotonergic components was analyzed by western blot and real-time PCR. Our results show that TLR9 activation inhibits serotonin transporter activity and expression, involving p38/MAPK and ERK/MAPK intracellular pathways, and reciprocally, serotonin increases TLR9 expression. Supporting this interaction, serotonin transporter, serotonin receptors and serotonin producer enzymes were found altered in intestinal tract of Tlr9 mice. We conclude that TLR9 could contribute to intestinal homeostasis by modulation of intestinal serotonergic system.
肠内 5-羟色胺能系统是肠道内稳态的关键调节者；然而，其调节机制尚不清楚。Toll 样受体 9（TLR9）作为先天免疫受体，可在肠道中检测到不同的外来物质，从而维持肠道完整性。由于对 TLR9 在肠道中的作用知之甚少，我们的目的是探讨 TLR9 与肠内 5-羟色胺能系统之间的潜在调节关系。本研究使用 Caco-2/TC7 细胞系和 Tlr9 敲除小鼠的肠道进行研究。进行了 5-羟色胺摄取研究，并通过 Western blot 和实时 PCR 分析了不同 5-羟色胺能成分的分子表达。我们的结果表明，TLR9 的激活抑制了 5-羟色胺转运体的活性和表达，涉及 p38/MAPK 和 ERK/MAPK 细胞内途径，而反过来，5-羟色胺又增加了 TLR9 的表达。支持这种相互作用，我们发现 Tlr9 敲除小鼠的肠道中 5-羟色胺转运体、5-羟色胺受体和 5-羟色胺产生酶发生了改变。我们的结论是，TLR9 可以通过调节肠内 5-羟色胺能系统来促进肠道内稳态。
