Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells
Schwab, M; Reynders, V; Shastri, Y; Loitsch, S; Stein, J; Schroeder, O
| HERO ID | 1456330 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells |
| Authors | Schwab, M; Reynders, V; Shastri, Y; Loitsch, S; Stein, J; Schroeder, O |
| Journal | Molecular Immunology |
| Volume | 44 |
| Issue | 8 |
| Page Numbers | 2107-2114 |
| Abstract | <strong>BACKGROUND AND AIMS: </strong>The human cathelicidin (LL-37) is one of the major antimicrobial peptides of the non-specific innate immune system in the intestinal tract. Altered expression has been associated with gastrointestinal disease. Recent studies demonstrated that butyrate induces LL-37 mRNA in colonic epithelial cells, however the underlying molecular mechanisms have not been elucidated. The objective of this study was to investigate the regulatory pathways involved in butyrate-induced up-regulation of LL-37.<br /><br /><strong>METHODS AND RESULTS: </strong>Treatment of Caco-2 and HT-29 cells with butyrate led to a time-dependent up-regulation of LL-37 mRNA expression as determined by semi-quantitative RT-PCR. Up-regulation of LL-37 mRNA by butyrate was subsequently followed by an increase in LL-37 protein expression as observed by immunofluorescence. Co-incubation of butyrate with a VDR, p38 MAPK, ERK 1/2 and TGF-beta1 receptor kinase inhibitor all reduced butyrate-mediated LL-37 mRNA up-regulation. In contrast, transfection of Caco-2 cells with a dominant-negative PPARgamma mutant vector did not affect butyrate-mediated up-regulation of LL-37 mRNA.<br /><br /><strong>CONCLUSION: </strong>Our results clearly demonstrate that butyrate-mediated up-regulation of LL-37 is influenced by several signalling pathways and receptors including MAPKs as well as VDR and TGF-beta1, but not by PPARgamma. These data may provide new opportunities in the treatment of gastrointestinal diseases. |
| Doi | 10.1016/j.molimm.2006.09.016 |
| Pmid | 17055059 |
| Wosid | WOS:000244351500033 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000244351500033 |
| Is Public | Yes |
| Language Text | English |
| Keyword | butyrate; cathelicidin; colon; innate immunity; LL-37; MAPK; PPAR gamma; TGF-beta 1; VDR |