Human Beta-Defensin 3 Is Up-Regulated in Cutaneous Leprosy Type 1 Reactions
نویسندگان
چکیده
BACKGROUND Leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy developed depends upon the host immune response. Type 1 reactions (T1Rs), that complicate borderline and lepromatous leprosy, are due to an increase in cell-mediated immunity and manifest as nerve damage and skin inflammation. Owing to the increase in inflammation in the skin of patients with T1Rs, we sought to investigate the activation of the innate immune system during reactionary events. Specifically, we investigated the expression levels of human beta-defensins (hBDs) 2 and 3 in the skin of patients with T1Rs, in keratinocytes, and in macrophages stimulated with M. leprae and corticosteroids. RESULTS Skin biopsies from twenty-three patients with Type 1 reactions were found to have higher transcript levels of hBD3 as compared to fifteen leprosy patients without Type 1 reactions, as measured by qPCR. Moreover, we observed that keratinocytes but not macrophages up-regulated hBD2 and hBD3 in response to M. leprae stimulation in vitro. Corticosteroid treatment of patients with T1Rs caused a suppression of hBD2 and hBD3 in skin biopsies, as measured by qPCR. In vitro, corticosteroids suppressed M. leprae-dependent induction of hBD2 and hBD3 in keratinocytes. CONCLUSIONS This study demonstrates that hBD3 is induced in leprosy Type 1 Reactions and suppressed by corticosteroids. Furthermore, our findings demonstrate that keratinocytes are responsive to M. leprae and lend support for additional studies on keratinocyte innate immunity in leprosy and T1Rs. TRIAL REGISTRATION Controlled-Trials.com ISRCTN31894035.
منابع مشابه
Comparison of the Effect of Alpha Lipoic Acid (ALA) and Beta-Defensin 1 Protein on Human Sperm Motility and Viability in Different Times of Incubation
Background and Objectives: Antioxidant alpha lipoic acid and β-defensin 1 protein may have a positive effect on the quality of sperm parameters. In this study, the effect of sperm incubation with alpha lipoic acid antioxidant and β-defensin 1 protein were assessed on sperm motility and viability at different times. Methods: In this experimental study, routine semen analysis was carried out o...
متن کاملP-24: Beta Defensin 126 and Its Role in Intra-Uterine Insemination Outcome
Background: Human β-defensin 126 is a small cationic glycoprotein that coats the plasma membrane of sperm during epididymal transit. It provides protection for sperms from infection-causing microbes and against the female immune system. Defensin remains on the sperm until sperm become capacitated in the female reproductive tract. DEFB126 gene is located on the subtelomeric end of 20p13 in human...
متن کاملBeta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells.
The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of beta-defensin expression by IEC. The effect of LPS a...
متن کاملChemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family.
Human defensins are natural peptide antibiotics. On the basis of the position and bonding of six conserved cysteine residues, they are divided into two families, designated alpha- and beta-defensins. Human alpha-defensins are expressed predominantly in neutrophils (human neutrophil peptides (HNP) 1-4) or intestinal Paneth cells (human defensins (HD) 5 and 6). Although alpha-defensins have been ...
متن کاملHuman beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity.
β-Defensins are antibiotic peptides involved in host defense at the epithelial surface. Three human β-defensins (hBDs)--hBD-1, hBD-2, and hBD-3--have been identified so far. We have characterized a new member of the β-defensin family, hBD-4, based on screening of genomic sequences and subsequent functional analysis. In contrast to hBD-1, hBD-2, and hBD-3, which are diffusely expressed throughou...
متن کامل