Inducible and Constitutive β-Defensins Are Differentially Expressed in Crohn's Disease and Ulcerative Colitis

Abstract

Antimicrobial peptides such as defensins provide nonspecific mucosal defense against a multitude of microorganisms. Recently, it has been shown that luminal bacteria may invade the mucosa in inflammatory bowel diseases, suggesting a defect in innate mucosal immunity. The aim of this study was to investigate the expression of human beta-defensins (HBD) in controls, Crohn's disease (CD), ulcerative colitis (UC), and unspecific inflammation. Up to 4 biopsies were taken from 103 patients (33 controls, 24 with Crohn's disease, 36 with ulcerative colitis, 10 with unspecific colitis). Mucosal mRNA was measured using real-time fluorescence temperature cycler reverse-transcription polymerase chain reaction with primers for HBD-1, HBD-2, HBD-3, tumor necrosis factor alpha, and interleukin 8. Mucosal HBD-1 expression was marginally decreased in both CD and UC. HBD-2 was increased exclusively in UC but not in CD. The expression of the novel defensin HBD-3 was strongly correlated with HBD-2 and also raised predominantly in UC. The expression of both inducible beta-defensins was enhanced in the state of inflammation. Expression of HBD-2 showed a weak correlation with interleukin 8 only in inflamed CD biopsies but not with tumor necrosis factor alpha. The missing induction of both inducible beta-defensins in CD as compared with UC may cause a defect in barrier function that predisposes to bacterial invasion.

Differential Regulation of β-Defensin Expression in Human Skin by Microbial Stimuli

“…However, the skin produces many antimicrobial peptides not induced by IL-1 (21). Although hBD-3 has been found in inflamed epithelia (9,13), the link between inflammation and hBD-3 expression was not defined on a molecular level.…”

“…In addition to monocyte-derived cells, lymphocytes also possess TLRs (27,28), and intraepithelial lymphocytes are present in the skin and other epithelial surfaces (29). Additional lymphocytes are recruited to chronically inflamed epithelia where induced expression of hBD-2 and hBD-3 is found (13). We asked whether lymphocytes could contribute to the induction of antimicrobial peptides in epithelia during inflammation.…”

Isoleucine, an Essential Amino Acid, Induces the Expression of Human <i>β</i> Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

“…While HBD1 is constitutively expressed, HBD2 and 3 are inducible defensins. These HBDs are known to show an altered expression under inflammatory conditions due to attacks by bacteria-derived polysaccharides or other intestinal inflammations [11][12][13][14]. However, the precise mechanisms regarding how the inducible HBDs are associated with such inflammation remains to be elucidated.…”

Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population

“…16 Evidence suggests that DEFB1 may play an important role during the course of infection as well as inflammation. 15,17,18 The cluster of human defensin genes including adefensin genes and at least four b-defensin genes is located in chromosome 8p22-23. 5 This region containing a number of genes related to the innate immunity and the nervous system shows a strikingly high polymorphic rate in the human population.…”