Catestatin, a neuroendocrine antimicrobial peptide, induces human mast cell migration, degranulation and production of cytokines and chemokines
Catestatin, a neuroendocrine antimicrobial peptide, induces human mast cell migration, degranulation and production of cytokines and chemokines
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DOI：
10.1111/j.1365-2567.2010.03395.x
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发表时间：
2011-04-01
期刊：
影响因子：
6.4
通讯作者：
Okumura, Ko
中科院分区：
文献类型：
--
作者：
Aung, Gyi;Niyonsaba, Francois;Okumura, Ko
P>Catestatin是一种影响人体自主神经功能的神经内分泌肽，最近被发现是一种皮肤抗菌肽。人类睾丸素具有三种单核苷酸多态性：Gly364Ser、Pro370Leu和Arg374Gln。鉴于有报道表明抗菌肽和神经肽可诱导肥大细胞活化，我们推测catestatin可能刺激人类肥大细胞的多种功能，从而参与皮肤炎症反应的调节。Catestatin及其自然变异引起人肥大细胞系LAD2和外周血源肥大细胞迁移、脱颗粒并释放白三烯C-4和前列腺素D-2和E-2。此外，catestatin增加肥大细胞内Ca2+的动员，并诱导促炎细胞因子/趋化因子的产生，如粒细胞-巨噬细胞集落刺激因子、单核细胞趋化蛋白-1/CCL2、巨噬细胞炎症蛋白-1 α /CCL3和巨噬细胞炎症蛋白-1 β /CCL4。我们对可能的细胞机制的评估表明，g蛋白、磷脂酶C和丝裂原活化蛋白激酶/细胞外信号调节激酶（ERK）参与了catestatin诱导的肥大细胞活化，百日咳毒素（g蛋白抑制剂）、U-73122（磷脂酶C抑制剂）和U0126 （ERK抑制剂）分别具有抑制作用。我们还发现人类肥大细胞在mRNA和蛋白水平上表达烟碱乙酰胆碱受体的α 7亚基。然而，考虑到α 7受体mRNA和α 7特异性抑制剂的沉默不会影响catestatin介导的肥大细胞激活，我们得出结论，该受体不太可能在catestatin对人肥大细胞的刺激中起作用。我们发现神经内分泌抗菌肽catestatin激活人肥大细胞，提示该肽可能具有免疫调节功能，并为神经内分泌和皮肤免疫系统之间提供了新的联系。
P>Catestatin, a neuroendocrine peptide with effects on human autonomic function, has recently been found to be a cutaneous antimicrobial peptide. Human catestatin exhibits three single nucleotide polymorphisms: Gly364Ser, Pro370Leu and Arg374Gln. Given reports indicating that antimicrobial peptides and neuropeptides induce mast cell activation, we postulated that catestatin might stimulate numerous functions of human mast cells, thereby participating in the regulation of skin inflammatory responses. Catestatin and its naturally occurring variants caused the human mast cell line LAD2 and peripheral blood-derived mast cells to migrate, degranulate and release leukotriene C-4 and prostaglandins D-2 and E-2. Moreover, catestatins increased intracellular Ca2+ mobilization in mast cells, and induced the production of pro-inflammatory cytokines/chemokines such as granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1/CCL2, macrophage inflammatory protein-1 alpha/CCL3 and macrophage inflammatory protein-1 beta/CCL4. Our evaluation of possible cellular mechanisms suggested that G-proteins, phospholipase C and the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) are involved in catestatin-induced mast cell activation as evidenced by the inhibitory effects of pertussis toxin (G-protein inhibitor), U-73122 (phospholipase C inhibitor) and U0126 (ERK inhibitor), respectively. We also found that human mast cells express the alpha 7 subunit of the nicotinic acetylcholine receptor at both the mRNA and protein levels. Given that silencing the alpha 7 receptor mRNA and an alpha 7-specific inhibitor did not affect catestatin-mediated activation of mast cells, however, we concluded that this receptor is not likely to be functional in human mast cell stimulation by catestatins. Our finding that the neuroendocrine antimicrobial peptide catestatin activates human mast cells suggests that this peptide might have immunomodulatory functions, and provides a new link between neuroendocrine and cutaneous immune systems.