TY - JOUR
T1 - Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli
AU - Schauber, Jürgen
AU - Dorschner, Robert A.
AU - Yamasaki, Kenshi
AU - Brouha, Brook
AU - Gallo, Richard L.
PY - 2006/8
Y1 - 2006/8
N2 - Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and β-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D 3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia but not in keratinocytes or monocytes. Distinct factors induced β-defensin expression. In all cell types, vitamin D3 activated the cathelicidin promoter and was dependent on a functional vitamin D responsive element. However, in colonic epithelia butyrate induced cathelicidin expression without increasing promoter activity and vitamin D3 activated the cathelicidin promoter without a subsequent increase in transcript accumulation. Induction of cathelicidin transcript correlated with increased processed mature peptide and enhanced antimicrobial activity against Staphylococcus aureus. However, induction of β-defensin-2 expression did not alter the innate antimicrobial capacity of cells in culture. These data suggest that antimicrobial peptide expression is regulated in a tissue-specific manner at transcriptional, post-transcriptional and post-translational levels. Furthermore, these data show for the first time that innate antimicrobial activity can be triggered independently of the release of other pro-inflammatory molecules, and suggest strategies for augmenting innate immune defence without increasing inflammation.
AB - Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and β-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D 3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia but not in keratinocytes or monocytes. Distinct factors induced β-defensin expression. In all cell types, vitamin D3 activated the cathelicidin promoter and was dependent on a functional vitamin D responsive element. However, in colonic epithelia butyrate induced cathelicidin expression without increasing promoter activity and vitamin D3 activated the cathelicidin promoter without a subsequent increase in transcript accumulation. Induction of cathelicidin transcript correlated with increased processed mature peptide and enhanced antimicrobial activity against Staphylococcus aureus. However, induction of β-defensin-2 expression did not alter the innate antimicrobial capacity of cells in culture. These data suggest that antimicrobial peptide expression is regulated in a tissue-specific manner at transcriptional, post-transcriptional and post-translational levels. Furthermore, these data show for the first time that innate antimicrobial activity can be triggered independently of the release of other pro-inflammatory molecules, and suggest strategies for augmenting innate immune defence without increasing inflammation.
KW - Cathelicidin
KW - Colon mucosa
KW - Defensin
KW - Gene regulation
KW - Human
KW - Skin
UR - http://www.scopus.com/inward/record.url?scp=33746087225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746087225&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2567.2006.02399.x
DO - 10.1111/j.1365-2567.2006.02399.x
M3 - Article
C2 - 16895558
AN - SCOPUS:33746087225
VL - 118
SP - 509
EP - 519
JO - Immunology
JF - Immunology
SN - 0019-2805
IS - 4
ER -