Abstracts of the 28th Spring Symposium of the German Society of Allergy and Clinical Immunology, Mainz, March 17th-18th, 2016

Abstracts of the 28th Spring Symposium of the German Society of Allergy and Clinical Immunology, Mainz, March 17th-18th, 2016
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德国过敏与临床免疫学学会第 28 届春季研讨会摘要,美因茨,2016 年 3 月 17-18 日

DOI:
10.1007/s40629-016-0094-4
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发表时间:
2016
影响因子:
--
通讯作者:
Pfützner W
Pfützner W
中科院分区:
--
文献类型:
--
作者:
Baum C;Möbs C;Pfützner W

文献摘要

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免疫皮肤病学和变态反应研究部,皮肤病学和变态反应系,汉诺威医学院,汉诺威,德国;药物和药物化学研究所,Heinrich海涅大学,Duesseldorf,德国。组胺受体是治疗特应性皮炎的可能的治疗靶结构。在特应性皮炎等过敏性皮肤病中,巨噬细胞被吸引到组织中,主要暴露于2种细胞因子以及过敏反应期间皮肤中释放的组胺。在这项研究中,我们研究了组胺对人单核细胞衍生的M2巨噬细胞在M-CSF的存在下分化并用IL-4或IL-13激活的作用。用定量PCR方法检测完全分化和IL-4激活的单核细胞衍生的M2巨噬细胞中H1 R、H2 R和H4 R mRNA的表达。我们观察到IL-4激活导致M2巨噬细胞中H1 R、H2 R和H4 R在mRNA水平上上调。用IL-4或IL-13激活M2巨噬细胞后,M2细胞趋化因子CCL 22和CCL 17在mRNA和蛋白水平上表达增加。有趣的是,组胺刺激导致CCL 17表达的显著进一步上调,而CCL 22的表达不受组胺影响。为了显示哪种组胺受体负责CCL 17的上调,我们刺激人IL-4或IL-13活化的M2巨噬细胞上的H1 R、H2 R和H4 R。令人惊讶的是,我们观察到这种效应归因于H2 R。e用氨苯海拉明和4-MH刺激H2 R(H2 R/H4 R激动剂)导致IL-4或IL-13激活的M2巨噬细胞中CCL 17在mRNA和蛋白水平上的显著上调,这可以令人信服地被前总之,我们通过上调M2巨噬细胞中的2种相关趋化因子CCL 17来显示H2 R的新功能这可能导致表达CCR 4的β 2细胞明显地被吸引到炎症侧,并为组胺支持β 2主导的环境的作用提供了证据。可能对特应性皮炎的病程和疾病的治疗有影响。
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Duesseldorf, Germany e histamine receptors are possible therapeutical target structures for the treatment of atopic dermatitis. In allergic skin diseases such as atopic dermatitis, macrophages are attracted into tissue and exposed mainly to 2 cytokines and also to histamine which is released in the skin during allergic reactions. In this study, we investigated the role of histamine on human monocyte derived M2 macrophages differentiated in the presence of M-CSF and activated with IL-4 or IL-13. H1R-H2R-and H4R mRNA expressions were measured on fully differentiated and IL-4 activated monocyte derived M2 macrophages by quantitative PCR. We observed that the activation with IL-4 led to an up-regulation of the H1R, H2R and H4R at mRNA level in M2 macrophages. e activation of M2 macrophages with IL-4 or IL-13 resulted in higher expression levels of the 2 cell attracting chemokines CCL22 and CCL17 at mRNA-and protein level. Interestingly, the stimulation with histamine led to a significant further up-regulation of CCL17 expression whereas the expression of CCL22 was not affected by histamine. To show which histamine receptor is responsible for the up-regulation of CCL17, we stimulated the H1R, H2R and H4R on human IL-4 or IL-13 activated M2 macrophages. Surprisingly, we observed that the effect was attributed to the H2R. e stimulation of the H2R with amthamine and 4-MH (H2R/H4R agonist) led to a significant up-regulation of the CCL17 expression at mRNA-and protein level in IL-4 or IL-13 activated M2 macrophages which could convincingly be blocked by pre-incubation with the specific H2R antagonist ranitidine.In summary we show a new function of the H2R by upregulating the 2 related chemokine CCL17 in M2 macrophages which might lead to a pronounced attraction of CCR4 expressing 2 cells into the side of inflammation and provide evidence for a role of histamine to support a 2 dominated milieu. is might have an impact on the course of atopic dermatitis and for the treatment of the disease.