| Autor: |
Schauber, J., Svanholm, C., Termén, S., Iffland, K., Menzel, T., Scheppach, W., Melcher, R., Agerberth, B., Lührs, H., Gudmundsson, G.H. |
| Předmět: |
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| Zdroj: |
Gut; May2003, Vol. 52 Issue 5, p735, 7p, 1 Diagram, 10 Graphs |
| Abstrakt: |
Background and aims: Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate rnucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated. Methods: LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored. Results: In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression. Conclusions: Expression of the cathelicidin LL-37 in colonocytes and cellular differentiation are separately modulated by SCFA via distinct signalling pathways. These data may provide a rationale for dietary modulation of mucosal defence mechanisms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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