Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne.
Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne.
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DOI：
10.1186/1471-5945-13-10
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发表时间：
2013-09-06
期刊：
影响因子：
--
通讯作者：
Langlands K
中科院分区：
文献类型：
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作者：
Selway JL;Kurczab T;Kealey T;Langlands K
痤疮是人类毛发皮脂腺单位的一种常见疾病，但角化过度和随后的炎症(粉刺形成)的机制仍未确定，尽管与皮肤病原体有关。此前有报道称，皮脂管中的角质形成细胞释放细胞因子白介素1α(IL-1α)在粉刺的生命周期中起关键作用，参与粉刺的发生和自然消退。Toll样受体是一类识别微生物呈现的病原体相关分子模式(PAMP)的分子，它启动一系列信号级联反应，最终释放抗菌化合物和细胞因子。我们采用体外皮脂腺和原代单层角质形成细胞培养，结合ELISA、免疫组织化学、Western blotting和RT-PCR等方法，探讨TLR激活在痤疮发病机制中的作用。我们发现TLR2在基底层角质形成细胞、漏斗状角质形成细胞和皮脂腺中均有表达，其激活可刺激体外培养的人原代角质形成细胞释放IL-1α。体外分离的人皮脂腺暴露于TLR2特异性α，在暴露7天后出现IL-1 PAMP样角化。角质形成细胞中TLR的激活和IL-1α的分泌可能是痤疮发生的始动步骤，因此对痤疮的病理生理学至关重要。
Acne is a common disorder of the human pilosebaceous unit, yet the mechanisms underlying hyperkeratinisation and subsequent inflammation (comedogenesis) remain to be determined, although cutaneous pathogens are implicated. Previously, it was reported that the release of the cytokine interleukin-1α (IL-1α) by keratinocytes of the sebaceous duct was pivotal in the life cycle of the comedone, mediating both its development and its spontaneous resolution. Toll-like receptors are a family of molecules that recognise pathogen associated molecular patterns (PAMPs) presented by microorganisms, initiating a signalling cascade terminating in the release of antimicrobial compounds and cytokines. We used ex vivo sebaceous gland and primary monolayer keratinocyte culture, alongside ELISAs, immunohistochemistry, Western blotting and RT-PCR to investigate the contribution of TLR activation to acne pathogenesis. We found TLR2 to be expressed in basal and infundibular keratinocytes, and sebaceous glands, and its activation provoked the release of IL-1α from primary human keratinocytes in vitro. The exposure of microdissected human sebaceous glands to PAMPs specific for TLR2 in vitro resulted in a pattern of IL-1α like cornification after seven days of exposure. TLR activation and secretion of IL-1α from keratinocytes may be initiating steps in comedogenesis and, therefore, critical to the pathophysiology of acne.