Beta-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 and peptidoglycan on beta-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of beta-defensin-2 was assessed using promoter-reporter constructs of the human beta-defensin-2 gene. LPS and peptidoglycan stimulated beta-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-kappaB or AP-1 site within the beta-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of beta-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide beta-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.
Vora
Puja
P
Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Youdim
Adrienne
A
Thomas
Lisa S
LS
Fukata
Masayuki
M
Tesfay
Samuel Y
SY
Lukasek
Katie
K
Michelsen
Kathrin S
KS
Wada
Akihiro
A
Hirayama
Toshiya
T
Arditi
Moshe
M
Abreu
Maria T
MT
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010457:Peptidoglycan / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis*
D000954:Antigens, Surface; C106641:DEFB4A protein, human; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D023083:beta-Defensins