Microbicidal protein psoriasin is a multifunctional modulator of neutrophil activation
Microbicidal protein psoriasin is a multifunctional modulator of neutrophil activation
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DOI：
10.1111/j.1365-2567.2007.02782.x
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发表时间：
2008-07
期刊：
影响因子：
6.4
通讯作者：
Yan Zheng;F. Niyonsaba;H. Ushio;S. Ikeda;I. Nagaoka;K. Okumura;H. Ogawa
中科院分区：
文献类型：
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作者：
Yan Zheng;F. Niyonsaba;H. Ushio;S. Ikeda;I. Nagaoka;K. Okumura;H. Ogawa
作为宿主防御中的效应细胞，中性粒细胞通过由氧化剂和抗微生物肽组成的有效抗微生物武器库主动破坏入侵微生物。银屑病是一种杀灭大肠杆菌的抗菌蛋白，已发现在银屑病中过表达，银屑病是一种以中性粒细胞浸润为特征的皮肤病。除了先前报道的杀微生物活性和中性粒细胞的趋化性之外，我们假设银屑病素可能调节其他中性粒细胞功能，如细胞因子和趋化因子的产生、活性氧的产生和抗菌肽的释放。在目前的研究中，我们证明银屑病素激活中性粒细胞产生一系列细胞因子和趋化因子，包括白细胞介素-6（IL-6）、IL-8/CXCL 8、肿瘤坏死因子-α、巨噬细胞炎性蛋白-1 α（MIP-1α）/CCL 3、MIP-1β/CCL 4和MIP-3α/CCL 20。此外，银屑病蛋白诱导促分裂原活化蛋白激酶p38和细胞外信号调节激酶（ERK）的磷酸化，但不诱导c-Jun N-末端激酶（JNK）的磷酸化，这两者都是产生细胞因子和趋化因子所必需的，如p38和ERK抑制剂对银屑病蛋白介导的中性粒细胞活化的抑制作用所证明的。此外，银肩病素刺激中性粒细胞产生活性氧，最有可能是通过烟酰胺腺嘌呤二核苷酸磷酸氧化酶活化。最后，我们证明银屑病增强α防御素（称为人中性粒细胞肽（HNP）1至3）的信使RNA表达，并诱导其细胞外释放。因此，除了其抗微生物特性之外，银肩病素还可以通过增强炎症或感染部位的中性粒细胞宿主防御功能来促进先天免疫。
As effector cells in host defence, neutrophils actively destroy invading microorganisms via a potent antimicrobial arsenal composed of oxidants and antimicrobial peptides. Psoriasin, an Escherichia coli‐cidal antimicrobial protein, has been found to be overexpressed in psoriasis, a skin disease characterized by infiltration of neutrophils. In addition to its microbicidal activities and chemotaxis of neutrophils reported previously, we hypothesized that psoriasin might regulate other neutrophil functions such as cytokine and chemokine production, reactive oxygen species generation, and release of antimicrobial peptides. In the current study, we demonstrate that psoriasin activates neutrophils to produce a range of cytokines and chemokines including interleukin‐6 (IL‐6), IL‐8/CXCL8, tumour necrosis factor‐α, macrophage inflammatory protein‐1α (MIP‐1α)/CCL3, MIP‐1β/CCL4 and MIP‐3α/CCL20. Furthermore, psoriasin induces phosphorylation of mitogen‐activated protein kinase p38 and extracellular signal‐regulated kinase (ERK), but not c‐Jun N‐terminal kinase (JNK), both of which are required for the production of cytokines and chemokines as evidenced by the inhibitory effects of p38 and ERK inhibitors on psoriasin‐mediated neutrophil activation. Moreover, psoriasin stimulates the generation of reactive oxygen species from neutrophils, most likely via nicotinamide adenine dinucleotide phosphate oxidase activation. Finally, we demonstrate that psoriasin enhances messenger RNA expression of α‐defensins, termed human neutrophil peptides (HNP) 1 to 3, and induces their extracellular release. Besides its antimicrobial properties, therefore, psoriasin may contribute to innate immunity through enhancing neutrophil host defence functions at sites of inflammation or infection.