The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders

TLDR

Epithelial surfaces act as a primary barrier against microbes, and antimicrobial peptides such as LL‑37, encoded by the single human CAMP gene, are increasingly recognized as key components of this defense system. The study investigates whether LL‑37 is up‑regulated in inflammatory skin disorders and proposes its protective role in maintaining skin barrier integrity. The authors used in situ hybridization and immunohistochemistry to localize LL‑37 mRNA and peptide in keratinocytes across the epidermis of inflamed skin. LL‑37, originally isolated from granulocytes, is up‑regulated in inflammatory skin disorders, is present in psoriatic scale fractions that show antibacterial activity, supporting a protective role for the peptide.

Abstract

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 (<i>CAMP</i> or cathelicidinantimicrobial 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 <i>in situ</i> 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.