Abstract：
Toll-like receptor 2 (TLR2) and galectin-3 (Gal-3) are involved in the pathological process of asthma, but the underlying mechanism is not fully understood. We hypothesized that TLR2 pathway may regulate expression of Gal-3 in allergic airway inflammation. Wild-type (WT) and TLR2-/- mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-21 to establish a model of allergic airway inflammation, and were treated with a specific ERK inhibitor U0126. Histological changes in the lungs were analyzed by hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining; cytokines and anti-OVA immunoglobulin E (IgE) were tested by ELISA; and related protein expression in lung tissues was measured by western blot. We found that the expression levels of TLR2 and Gal-3 markedly increased concomitantly with airway inflammation after OVA induction, while TLR2 deficiency significantly alleviated airway inflammation and reduced Gal-3 expression. Moreover, the expression levels of phosphorylated mitogen-activated protein kinases (p-MAPKs) were significantly elevated in OVA-challenged WT mice, while TLR2 deficiency only significantly decreased phosphorylated extracellular signal-regulated kinase (p-ERK) levels. Furthermore, we found that U0126 treatment significantly alleviated allergic airway inflammation and decreased Gal-3 levels in OVA-challenged WT mice, but had no further effect in OVA-challenged TLR2-/- mice. These above results suggested that TLR2 is an upstream signal molecule of ERK. We further demonstrated that TLR2 regulates Gal-3 expression through the ERK pathway in LTA-stimulated macrophages in vitro. Our findings showed that the TLR2-ERK signaling pathway regulates Gal-3 expression in a murine model of allergic airway inflammation.
摘要：
Toll样受体2(TLR2)和半乳糖凝集素-3(Gal-3)参与哮喘的病理过程,但是潜在的机制还没有完全理解。我们假设TLR2通路可能在过敏性气道炎症中调节Gal-3的表达。第0天对野生型(WT)和TLR2-/-小鼠致敏,第14-21天用卵清蛋白(OVA)攻击,建立过敏性气道炎症模型,并用特异性ERK抑制剂U0126治疗。采用苏木精-伊红(HE)和高碘酸-席夫氏(PAS)染色分析肺组织的组织学变化;采用ELISA检测细胞因子和抗OVA免疫球蛋白E(IgE);采用Westernblot检测肺组织中相关蛋白的表达。我们发现，TLR2和Gal-3的表达水平在OVA诱导后伴随气道炎症而显著增加，而TLR2缺乏可显着减轻气道炎症并降低Gal-3表达。此外，磷酸化丝裂原活化蛋白激酶（p-MAPK）的表达水平在OVA攻击的WT小鼠中显著升高，而TLR2缺乏仅显著降低磷酸化的细胞外信号调节激酶(p-ERK)水平。此外，我们发现U0126治疗可显着缓解OVA攻击的WT小鼠的过敏性气道炎症和Gal-3水平降低，但在OVA攻击的TLR2-/-小鼠中没有进一步的作用。上述结果表明TLR2是ERK的上游信号分子。我们进一步证明，TLR2在LTA刺激的巨噬细胞中通过ERK途径调节Gal-3表达。我们的发现表明TLR2-ERK信号通路调节小鼠过敏性气道炎症模型中Gal-3的表达。
