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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Syk inhibitor R406 downregulates inflammation in an in vitro model of Pseudomonas aeruginosa infection
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Syk inhibitor R406 downregulates inflammation in an in vitro model of Pseudomonas aeruginosa infection

机译：SYK抑制剂R406在铜绿假单胞菌铜绿假单胞菌感染的体外模型中下调炎症

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As Pseudomonas aeruginosa infections are characterized by strong inflammation of infected tissues, anti-inflammatory therapies in combination with antibiotics have been considered for the treatment of associated diseases. Syk tyrosine kinase is an important regulator of inflammatory responses, and its specific inhibition was explored as a therapeutic option in several inflammatory conditions; however, this has not been studied in bacterial infections. We used a model of in vitro infection of human monocytic cell line THP-1 and lung epithelial cell line H292 with both wild-type and flagella-deficient mutant of P. aeruginosa strain K, as well as with clinical isolates from cystic fibrosis patients, to study the effect of a small molecule Syk inhibitor R406 on inflammatory responses induced by this pathogen. One-hour pretreatment of THP-1 cells with 10 mu mol/L R406 resulted in a significant downregulation of the expression of the adhesion molecule ICAM-1, pro-inflammatory cytokines TNF-alpha and IL-1 beta, and phosphorylated signaling proteins ERK2, JNK, p-38, and I kappa B alpha, as well as significantly decreased TNF-alpha release by infected H292 cells. The results suggest that Syk is involved in the regulation of inflammatory responses to P. aeruginosa, and R406 may potentially be useful in dampening the damage caused by severe inflammation associated with this infection.
机译：由于铜绿假单胞菌感染的特点是感染组织发生强烈炎症，因此，抗炎疗法与抗生素联合应用已被考虑用于治疗相关疾病。Syk酪氨酸激酶是一种重要的炎症反应调节因子，其特异性抑制被认为是几种炎症条件下的一种治疗选择；然而，这还没有在细菌感染中进行研究。我们利用人单核细胞系THP-1和肺上皮细胞系H292与铜绿假单胞菌K株野生型和鞭毛缺陷突变株以及囊性纤维化患者临床分离株的体外感染模型，研究小分子Syk抑制剂R406对该病原体诱导的炎症反应的影响。用10μmol/L R406预处理THP-1细胞一小时后，粘附分子ICAM-1、促炎细胞因子TNF-α和IL-1β、磷酸化信号蛋白ERK2、JNK、p-38和I-κB-α的表达显著下调，感染的H292细胞释放TNF-α的量显著降低。结果表明，Syk参与调节对铜绿假单胞菌的炎症反应，R406可能有助于减轻与这种感染相关的严重炎症造成的损害。

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