Sand fly saliva presents molecules with potential to development of compounds for treatment of inflammatory diseases. Agaphelin, isolated from the saliva of the mosquito Anopheles gambiae, demonstrates anti-inflammatory properties such as neutrophils chemotaxis inhibition. Here, we extend these results and evaluated the role of agaphelin (0.1−100 nM) in an in vitro model consisting in the activation of human bronchial epithelial cells (BEAS-2B) by IL-4 (50 ng/mL) or lipopolysaccharide (LPS; 10 ng/mL). Agaphelin is non-cytotoxic for BEAS-2B cells. Notably, agaphelin markedly reduces CCL2 and IL-8 production induced by IL-4 or LPS, without altering the IL-10 production. The TLR4 expression and STAT1 phosphorylation induced by LPS were inhibited by agaphlin. In addition, agaphelin decreased the phosphorylation of STAT6 induce by IL-4, whose effect was independent of IL-4-binding activity. Taken together, these findings identify agaphelin as a potential anti-inflammatory therapeutic agent for airway inflammations.

沙蝇唾液呈现出具有开发用于治疗炎症疾病的化合物的潜力的分子。从冈比亚按蚊的唾液中分离出的 Agaphelin ，显示抗炎特性，例如中性粒细胞趋化性抑制。在这里，我们扩展了这些结果并评估了 agaphelin (0.1-100 nM) 在体外模型中的作用，该模型包括通过 IL-4 (50 ng/mL) 或脂多糖激活人支气管上皮细胞 (BEAS-2B)。 LPS；10 纳克/毫升）。Agaphelin 对 BEAS-2B 细胞无细胞毒性。值得注意的是，agaphelin 显着降低了由 IL-4 或 LPS 诱导的 CCL2 和 IL-8 的产生，而不会改变 IL-10 的产生。LPS诱导的TLR4表达和STAT1磷酸化被agaphlin抑制。此外，agaphelin 降低了 IL-4 诱导的 STAT6 磷酸化，其作用与 IL-4 结合活性无关。总之，这些发现将 agaphelin 鉴定为气道炎症的潜在抗炎治疗剂。