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Departments of
*
General Surgery and
Pulmonology, Maastricht University, Maastricht, The Netherlands
The acute phase proteins LPS binding protein (LBP) and serum
amyloid A (SAA) are produced by the liver and are present in the
circulation. Both proteins have been shown to participate in the immune
response to endotoxins. The intestinal mucosa forms a large surface
that is continuously exposed to these microbial products. By secretion
of antimicrobial and immunomodulating agents, the intestinal epithelium
contributes to the defense against bacteria and their products. The aim
of this study was to explore the influence of the inflammatory
mediators TNF-
, IL-6, and IL-1ß on the release of LBP and SAA by
intestinal epithelial cells (IEC). In addition, the induction of LBP
and SAA release by cell lines of intestinal epithelial cells and
hepatic cells was compared. The data obtained show that in addition to
liver cells, IEC also expressed LBP mRNA and released bioactive LBP and
SAA upon stimulation. Regulation of LBP and SAA release by IEC and
hepatocytes was typical for class 1 acute phase proteins, although
differences in regulation between the cell types were observed.
Endotoxin did not induce LBP and SAA release. Glucocorticoids were
demonstrated to strongly enhance the cytokine-induced release of LBP
and SAA by IEC, corresponding to hepatocytes. The data from this study,
which imply that human IEC can produce LBP and SAA, suggest a role for
these proteins in the local defense mechanism of the gut to endotoxin.
Furthermore, the results demonstrate that tissues other than the liver
are involved in the acute phase response.
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