OBJECTIVE: Allergic diseases are a group of immune-mediated disorders mainly caused by an immunoglobulin E (IgE)-dependent immunological response to an innocuous allergen. Therefore, this study aimed to investigate the effect of leaves and pseudostems extract of turmeric (TLSWE-8510) on IgE/bovine serum albumin (BSA)-stimulated allergic responses in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice.
METHODS: The effect of TLSWE-8510 on mast cell degranulation has been evaluated by investigating the release of β-hexosaminidase and histamine in IgE/BSA-stimulated BMCMCs. Additionally, anti-allergic properties of TLSWE-8510 on IgE/BSA-stimulated BMCMCs were investigated using suppression of nuclear factor-kappa B (NF-κB), and spleen tyrosine kinase (Syk)-linker for T-cell activation (LAT)-extracellular-signal-regulated kinase (ERK)-GRB2 associated binding protein 2 (Gab2) signaling pathway and downregulation of allergy-related cytokines and chemokines expression. Furthermore, in vivo, studies were conducted using IgE-mediated PCA in BALB/c mice.
RESULTS: TLSWE-8510 treatment significantly inhibited the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of β-hexosaminidase and histamine dose-dependently. Additionally, TLSWE-8510 reduced the expression of high-affinity IgE receptors (Fc epsilon receptor I-FcεRI) on the surface of BMCMCs and the binding of IgE to FcεRI. Besides, the expression of cytokines and chemokines is triggered by IgE/BSA stimulation via activating the allergy-related signaling pathways. TLSWE-8510 dose-dependently downregulated the mRNA expression and the production of allergy-related cytokines (interleukin (IL)-1β, IL-3, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ), and chemokines (thymus and activation-regulated chemokine (TARC), and regulated upon activation, normal T cell expressed and secreted (RANTES)) by regulating the phosphorylation of downstream signaling molecules, NF-κB, and Syk, LAT, ERK and Gab2 in IgE/BSA-stimulated BMCMCs. Moreover, PCA reaction in IgE/BSA-stimulated BALB/c mice ears was effectively decreased by TLSWE-8510 treatment in a dose-dependent manner.
CONCLUSIONS: These results collectively demonstrated that TLSWE-8510 suppressed mast cell degranulation by inhibiting the release of chemical mediators related to allergies. TLSWE-8510 downregulated the allergy-related cytokines and chemokines expression and phosphorylation of downstream signaling molecules in IgE/BSA-stimulated BMCMCs. Furthermore, in vivo studies with IgE-mediated PCA reaction in the BALB/c mice ears were attenuated by TLSWE-8510 treatment. These findings revealed that TLSWE-8510 has the potential as a therapeutic agent for the treatment of allergic diseases.
目的:过敏性疾病是一组免疫介导的疾病,主要由免疫球蛋白E(IgE)依赖性免疫应答对一种无害的过敏原引起。因此,这项研究旨在研究姜黄叶和假茎提取物(TLSWE-8510)对IgE/牛血清白蛋白(BSA)刺激的小鼠骨髓来源的肥大细胞(BMCMC)和被动皮肤过敏的影响。BALB/c小鼠的反应(PCA)。
方法:通过研究IgE/BSA刺激的BMCMC中β-己糖胺酶和组胺的释放,评估了TLSWE-8510对肥大细胞脱颗粒的影响。此外,使用抑制核因子-κB(NF-κB)研究了TLSWE-8510对IgE/BSA刺激的BMCMC的抗过敏特性,和脾酪氨酸激酶(Syk)-T细胞活化(LAT)-细胞外信号调节激酶(ERK)-GRB2相关结合蛋白2(Gab2)信号通路和下调过敏相关细胞因子和趋化因子的表达。此外,在体内,在BALB/c小鼠中使用IgE介导的PCA进行研究。
结果:TLSWE-8510处理通过剂量依赖性地抑制β-氨基己糖苷酶和组胺的释放,显著抑制IgE/BSA刺激的BMCMC的脱颗粒。此外,TLSWE-8510降低了BMCMC表面上高亲和力IgE受体(Fcε受体I-FcεRI)的表达以及IgE与FcεRI的结合。此外,细胞因子和趋化因子的表达是由IgE/BSA刺激通过激活过敏相关的信号通路而触发的。TLSWE-8510剂量依赖性地下调mRNA表达和过敏相关细胞因子(白细胞介素(IL)-1β,IL-3,IL-4,IL-5,IL-6,IL-13,肿瘤坏死因子(TNF)-α,和干扰素(IFN)-γ),和趋化因子(胸腺和活化调节趋化因子(TARC),并在激活时受到调节,正常T细胞表达和分泌(RANTES))通过调节下游信号分子的磷酸化,NF-κB,还有Syk,LAT,IgE/BSA刺激的BMCMC中的ERK和Gab2。此外,通过TLSWE-8510处理,IgE/BSA刺激的BALB/c小鼠耳朵中的PCA反应以剂量依赖性方式有效降低。
结论:这些结果共同表明,TLSWE-8510通过抑制与过敏相关的化学介质的释放来抑制肥大细胞脱颗粒。TLSWE-8510下调IgE/BSA刺激的BMCMC中与过敏相关的细胞因子和趋化因子的表达和下游信号分子的磷酸化。此外,在BALB/c小鼠耳朵中IgE介导的PCA反应的体内研究通过TLSWE-8510处理减弱。这些发现揭示了TLSWE-8510具有作为治疗过敏性疾病的治疗剂的潜力。