Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation
Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation
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鉴定源自 ADP-核糖基化因子 1 (ARF1) 的肽最小区域，抑制 IgE 介导的肥大细胞活化
DOI：
10.1016/j.molimm.2018.11.002
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发表时间：
2019
影响因子：
3.6
通讯作者：
Nishida Keigo
中科院分区：
文献类型：
--
作者：
Uchida Ryota;Egawa Tomonori;Fujita Yoshio;Furuta Kazuyuki;Taguchi Hiroaki;Tanaka Satoshi;Nishida Keigo
肥大细胞在过敏反应和炎症中起着关键作用。高亲和力IgE受体（FcεRI）的聚集最终导致颗粒成分如组胺的释放，以及炎症细胞因子和脂质介质的新合成。这些物质与过敏和炎症的发展有关。因此，肥大细胞活化的有效抑制剂在治疗上是有益的。我们之前证明了从小GTPase ARF1 （adp -核糖基化因子1）的nh2末端区域（2-17:GNIFANLFKGLFGKKE）合成的肽抑制fcε ri诱导的肥大细胞脱颗粒。然而，ARF1肽nh2末端的构效关系尚未得到详细的研究。此外，ARF1的nh2末端肽是否抑制fcε ri诱导肥大细胞产生细胞因子和脂质介质，如白三烯C4 (LTC4)，目前尚不清楚。本研究表明，氨基酸残基k10 - k16是ARF1肽有效抑制fc4 - ri诱导的骨髓源性肥大细胞（BMMCs）活化所必需的，表现为肥大细胞脱颗粒、细胞因子分泌和白三烯释放减少。此外，我们发现ARF1肽抑制ige介导的被动皮肤过敏反应。我们的研究结果表明，ARF1衍生的肽可以发展成为一种新的抗过敏药物，用于过敏和肥大细胞相关疾病的治疗干预。
Mast cells play a pivotal role in allergic reactions and inflammations. Aggregation of the high affinity IgE receptor (FcεRI) eventually leads to the release of granule components such as histamine, as well as thede novosynthesis of inflammatory cytokines and lipid mediators. These substances are involved in the development of allergy and inflammation. Therefore, efficient inhibitors of mast cell activation would be therapeutically beneficial. We previously demonstrated that the synthetic peptide derived from the NH2-terminal region (2–17: GNIFANLFKGLFGKKE) of a small GTPase ARF1 (ADP-ribosylation factor1) inhibited FcεRI-induced mast cell degranulation. However, detailed structure-activity relationship study of NH2-terminal portion of ARF1 peptide has not been done. In addition, it is still unclear whether the NH2-terminal peptide of ARF1 suppresses FcεRI-induced production of cytokines and lipid mediators such as leukotriene C4 (LTC4) from mast cells.Here we show that amino acid residues K10-K16are necessary for ARF1 peptide to efficiently inhibit FcεRI-induced activation of bone marrow-derived mast cells (BMMCs), indicated by decreased mast cell degranulation, cytokine secretion and leukotriene release. Furthermore, we show that ARF1 peptide inhibits IgE-mediated passive cutaneous anaphylaxis reaction. Our results suggest that the peptide derived from ARF1 could be developed into a novel anti-allergic agent for therapeutic intervention in allergy and mast cell-related pathologies.