The human antimicrobial peptide dermcidin activates normal human keratinocytes
The human antimicrobial peptide dermcidin activates normal human keratinocytes
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DOI：
10.1111/j.1365-2133.2008.08925.x
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发表时间：
2009-02-01
影响因子：
10.3
通讯作者：
Okumura, K.
中科院分区：
文献类型：
--
作者：
Niyonsaba, F.;Suzuki, A.;Okumura, K.
皮肤已经进化出上皮防御机制，其特征在于抗微生物肽，其抑制各种微生物并表现出桥接先天免疫和适应性免疫的刺激活性。皮杀菌素（DCD）是一种新分离的由皮肤外分泌汗腺产生的抗菌肽。最近，DCD肽DCD-1和DCD-1 L已显示出对细菌和病毒的体外杀菌活性。由于一些皮肤来源的抗菌肽激活角质形成细胞，我们研究DCD-1 L是否也会激活角质形成细胞。通过酶联免疫吸附试验测定DCD-1 L诱导角质形成细胞产生细胞因子/趋化因子的能力，并使用各种抑制剂来研究DCD-1 L的刺激机制。Western blotting分析丝裂原活化蛋白激酶（MAPK）磷酸化和NF-κ B活化。DCD-1 L刺激角质形成细胞产生细胞因子和趋化因子，包括肿瘤坏死因子-α、白细胞介素-8（CXCL 8）、干扰素诱导蛋白10（CXCL 10）和巨噬细胞炎性蛋白-3 α（CCL 20）。为了确定所涉及的分子机制，我们发现DCD-1 L介导的细胞因子/趋化因子的产生受G蛋白和MAPK途径的控制，百日咳毒素和p38和ERK特异性抑制剂对DCD-1 L诱导的角质形成细胞活化的抑制作用证明了这一点。此外，我们证实，DCD-1 L可以诱导p38和ERK的磷酸化，并显着上调NF-κ B B activation.Taken在一起，DCD-1 L的新活性，刺激角质形成细胞的细胞因子/趋化因子的生产提供了新的证据表明，DCD，除了其杀菌能力，在皮肤免疫。
The skin has evolved an epithelial defence mechanism which is characterized by antimicrobial peptides that inactivate various microorganisms and exhibit stimulatory activities bridging innate and adaptive immunity. Dermcidin (DCD) is a newly isolated antimicrobial peptide produced by the eccrine sweat glands in the skin. Recently, the DCD peptides DCD-1 and DCD-1L have been shown to display in vitro microbicidal activities against bacteria and viruses.Because some skin-derived antimicrobial peptides activate keratinocytes, we investigated whether DCD-1L would also trigger keratinocyte activation.Normal human keratinocytes were used in this study. The ability of DCD-1L to induce the production of cytokines/chemokines by keratinocytes was determined by enzyme-linked immunosorbent assay, and various inhibitors were used to investigate the stimulatory mechanism of DCD-1L. Mitogen-activated protein kinase (MAPK) phosphorylation and NF-kappa B activation were analysed by Western blotting.DCD-1L stimulated keratinocytes to generate cytokines and chemokines including tumour necrosis factor-alpha, interleukin-8 (CXCL8), interferon-inducible protein 10 (CXCL10) and macrophage inflammatory protein-3 alpha (CCL20). To determine the molecular mechanism involved, we showed that DCD-1L-mediated cytokine/chemokine production was controlled by both G-protein and MAPK pathways, as evidenced by the inhibitory effects of pertussis toxin and specific inhibitors for p38 and ERK, but not for JNK, on DCD-1L-induced keratinocyte activation. Furthermore, we confirmed that DCD-1L could induce phosphorylation of p38 and ERK, and noticeably upregulated NF-kappa B activation.Taken together, the new activity of DCD-1L to stimulate the production of cytokines/chemokines by keratinocytes provides novel evidence for the implication of DCD, beyond its microbicidal ability, in skin immunity.