Role of macrophage migration inhibitory factor (MIF) in pollen-induced allergic conjunctivitis and pollen dermatitis in mice.

Role of macrophage migration inhibitory factor (MIF) in pollen-induced allergic conjunctivitis and pollen dermatitis in mice.
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DOI:
10.1371/journal.pone.0115593
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Shimizu T
Shimizu T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nagata Y;Yoshihisa Y;Matsunaga K;Rehman MU;Kitaichi N;Shimizu T

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花粉是临床上重要的空气过敏原,也是过敏性结膜炎的主要原因之一。也已知患有特应性皮炎(AD)的患者亚群在与花粉接触后会加剧面部的皮疹,特别是眼睑周围。这种花粉引起的皮肤反应现在被称为花粉皮炎。巨噬细胞移动抑制因子(MIF)是一种多能性细胞因子,在过敏性炎症中起重要作用。最近的研究结果表明,MIF参与了几种过敏性疾病,包括AD。在这项研究中,MIF敲除(KO),MIF转基因(Tg)和WT同窝小鼠免疫豚草(RW)花粉或日本雪松(JC)花粉,并通过滴眼液攻击。我们观察到,与WT小鼠或MIF KO小鼠相比,RW和JC花粉致敏的MIF Tg中结膜和眼睑浸润嗜酸性粒细胞的数量显著增加。在花粉致敏的MIF Tg小鼠眼睑皮肤部位,eotaxin、白细胞介素(IL)-5和IL-13的mRNA表达水平增加。体外分析表明,高嗜酸性粒细胞趋化因子的表达诱导真皮成纤维细胞的MIF与IL-4或IL-13的刺激相结合。在成纤维细胞中用CD 74 siRNA处理可抑制该嗜酸性粒细胞趋化因子表达。这些结果表明,MIF可以诱导嗜酸性粒细胞聚集在结膜和眼睑真皮暴露于花粉。因此,靶向抑制MIF可能成为控制花粉诱导的过敏性结膜炎和花粉皮炎的新选择。
Pollen is a clinically important airborne allergen and one of the major causes of allergic conjunctivitis. A subpopulation of patients with atopic dermatitis (AD) are also known to have exacerbated skin eruptions on the face, especially around the eyelids, after contact with pollen. This pollen-induced skin reaction is now known as pollen dermatitis. Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including AD. In this study, MIF knockout (KO), MIF transgenic (Tg) and WT littermate mice were immunized with ragweed (RW) pollen or Japanese cedar (JC) pollen and challenged via eye drops. We observed that the numbers of conjunctiva- and eyelid-infiltrating eosinophils were significantly increased in RW and JC pollen-sensitized MIF Tg compared with WT mice or MIF KO mice. The mRNA expression levels of eotaxin, interleukin (IL)-5 and IL-13 were increased in pollen-sensitized eyelid skin sites of MIF Tg mice. An in vitro analysis revealed that high eotaxin expression was induced in dermal fibroblasts by MIF combined with stimulation of IL-4 or IL-13. This eotaxin expression was inhibited by the treatment with CD74 siRNA in fibroblasts. These findings indicate that MIF can induce eosinophil accumulation in the conjunctiva and eyelid dermis exposed to pollen. Therefore, targeted inhibition of MIF might result as a new option to control pollen-induced allergic conjunctivitis and pollen dermatitis.
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