The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders
The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders
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DOI：
10.1074/jbc.272.24.15258
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发表时间：
1997-06-13
影响因子：
4.8
通讯作者：
Gudmundsson, GH
中科院分区：
文献类型：
--
作者：
Frohm, M;Agerberth, B;Gudmundsson, GH
上皮细胞构成了环境的主要屏障，并提供了抵御入侵微生物的第一道防线。抗微生物肽一般作为上皮屏障防御系统的参与者而出现，最初我们从粒细胞中分离出人抗微生物肽LL-37。基因编码该肽的CAMP（cathelicidin antimicrobial peptide）属于cathelicidin家族，其成员含有cathelin类型的保守前体部分，人类基因组似乎只有一个该家族的基因，而一些哺乳动物物种有几个cathelicidin基因，在本工作中，我们证明了该人类cathelicidin基因在炎性皮肤病中的上调，而在正常皮肤中未发现诱导。通过原位杂交和免疫组织化学，转录本和肽定位于整个炎症区域表皮的角质形成细胞中。此外，通过免疫印迹法在来自银屑病鳞屑的部分纯级分中检测到肽。这些馏分也表现出抗菌活性。我们提出LL-37的保护作用，当皮肤屏障的完整性受损时，参与第一道防线，并防止微生物的局部感染和全身入侵。
The epithelia constitute a major barrier to the environment and provide the first line of defense against invading microbes. Antimicrobial peptides are emerging as participants in the defense system of epithelial barriers in general, Originally we isolated the human antimicrobial peptide LL-37 from granulocytes. The gene (CAMP or cathelicidin antimicrobial peptide) coding for this peptide belongs to the cathelicidin family, whose members contain a conserved pro-part of the cathelin type, The human genome seems to have only one gene of this family, whereas some mammalian species have several cathelicidin genes, In the present work we demonstrate up-regulation of this human cathelicidin gene in inflammatory skin disorders, whereas in normal skin no induction was found, By in situ hybridization and immunohistochemistry the transcript and the peptide were located in keratinocytes throughout the epidermis of the inflammatory regions. In addition, the peptide was detected in partially pure fractions derived from psoriatic scales by immunoblotting. These fractions also exhibited antibacterial activity. We propose a protective role for LL-37, when the integrity of the skin barrier is damaged, participating in the first Line of defense, and preventing local-infection and systemic invasion of microbes.