通过抑制天冬氨酸半胱氨酸蛋白酶-1(caspase-1)的激活来抑制白细胞介素-32(IL-32)和胸腺基质淋巴细胞生成素(TSLP)的产生,从而减轻变应性鼻炎动物模型的炎症反应。

Inhibition of IL-32 and TSLP production through the attenuation of caspase-1 activation in an animal model of allergic rhinitis by Naju Jjok (Polygonum tinctorium).

机构信息

Biochip Research Center and Inflammatory Diseases Research Center, Hoseo University, Asan, Chungnam 336-795, Republic of Korea.

出版信息

Int J Mol Med. 2014 Jan;33(1):142-50. doi: 10.3892/ijmm.2013.1548. Epub 2013 Nov 5.

Abstract

In this study, we investigated the effects of Naju Jjok (Polygonum tinctorium Lour., NJJ) on interleukin (IL)-32 and thymic stromal lymphopoietin (TSLP) levels associated with allergic rhinitis (AR). Using female BALB/c mice, we created an animal model of ovalbumin (OVA)-induced AR. Prior to the callenge with OVA, the mice were administered, either nasally or orally with NJJ. In addition, we also used the eosinophilic cells line, Eol-1, stimulated with granulocyte‑macrophage colony-stimulation factor (GM-CSF). The mRNA and protein levels of inflammatory cytokines and markers [interleukin (IL)-32, IL-4, macrophage-inflammatory protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2)] were measured by RT-PCR and western blot analysis, respectively and serum levels were measured by ELISA. The increased levels of IL-32 in the mice with AR and in the stimulated eosinophilic cell line, Eol-1, were significantly reduced by NJJ. TSLP levels were also decreased following the oral administration of NJJ. Mice orally administered NJJ showed markedly alleviated clinical symptoms, such as a reduced number of nasal rubs, decreased spleen weight, decreased serum immunoglobulin E (IgE) levels and decreased serum histamine levels. The oral administration of NJJ significantly decreased the IL-4 levels, while increasing the interferon-γ levels in the spleen. The increased number of eosinophils and mast cells infiltrating the nasal mucosal tissue of the mice with AR were decreased following the oral administration of NJJ. NJJ effectively attenuated caspase-1 activity in the mice with AR and in the stimulated Eol-1 cells. The oral administration of NJJ significantly reduced the levels of inflammatory markers, such as MIP-2, ICAM-1 and COX-2. Furthermore, the intranasal administration of NJJ significantly reduced the early phase response to allergen exposure, such as nasal rubs, IgE production and histamine release, as well as the late phase responses, such as the expression of inflammatory markers. In conclusion, these data demonstrate that NJJ may play a regulatory role in nasal inflammation.

摘要

在这项研究中,我们研究了那如金(Polygonum tinctorium Lour.,NJJ)对与过敏性鼻炎(AR)相关的白细胞介素(IL)-32 和胸腺基质淋巴细胞生成素(TSLP)水平的影响。我们使用雌性 BALB/c 小鼠创建了卵清蛋白(OVA)诱导的 AR 动物模型。在接受 OVA 挑战之前,通过鼻腔或口服给予 NJJ。此外,我们还使用嗜酸性粒细胞系 Eol-1 刺激粒细胞-巨噬细胞集落刺激因子(GM-CSF)。通过 RT-PCR 和 Western blot 分析分别测量炎性细胞因子和标志物[白细胞介素(IL)-32、IL-4、巨噬细胞炎症蛋白-2(MIP-2)、细胞间黏附分子-1(ICAM-1)和环氧化酶-2(COX-2)]的 mRNA 和蛋白水平,并通过 ELISA 测量血清水平。AR 小鼠和受刺激的嗜酸性粒细胞系 Eol-1 中 IL-32 水平的升高,经 NJJ 治疗后显著降低。口服 NJJ 后 TSLP 水平也降低。口服 NJJ 的小鼠表现出明显的临床症状缓解,例如减少鼻摩擦次数、减少脾脏重量、降低血清免疫球蛋白 E(IgE)水平和降低血清组胺水平。口服 NJJ 可显著降低 IL-4 水平,同时增加脾脏中干扰素-γ水平。口服 NJJ 可减少 AR 小鼠鼻黏膜组织中嗜酸性粒细胞和肥大细胞的浸润。NJJ 可有效抑制 AR 小鼠和受刺激的 Eol-1 细胞中半胱天冬酶-1 的活性。口服 NJJ 可显著降低炎性标志物的水平,如 MIP-2、ICAM-1 和 COX-2。此外,鼻内给予 NJJ 可显著减少过敏原暴露的早期反应,如鼻摩擦、IgE 产生和组胺释放,以及晚期反应,如炎性标志物的表达。总之,这些数据表明 NJJ 可能在鼻炎症中起调节作用。

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