Goblet cell depletion occurs in various forms of colitis, but its mechanism is unknown. We have investigated two linked hypotheses: (i) that bacterial peptides, such as formyl-methionyl-leucyl-phenylalanine (fMLP), interact with epithelial cells inducing the release of chemokines, including interleukin-8 (IL-8), which in turn leads to the recruitment of neutrophils which release mucin secretagogues; (ii) that fMLP acts directly on epithelial cells to cause mucus secretion. Studies were performed to measure the effects of fMLP on the synthesis and secretion of IL-8 and mucus by the goblet cell differentiated colon cancer cell lines HT29-MTX (methotrexate-conditioned HT29 colonic adenocarcinoma cell line) and LS174T, and to assess the effects of neutrophil-derived secretagogues on goblet cell secretion in these cell lines. fMLP (0.1μM) increased the secretion of IL-8 by 105% (P < 0.0001) in HT29-MTX cells and by 401% (P < 0.0001) in LS174T cells. fMLP also increased the synthesis and secretion of mucins by these cell lines, with maximal effects of 65% above control values for synthesis (P < 0.01) and 73% for secretion (P < 0.01). A dose-related increase (up to 67%; P < 0.01) in mucin secretion was demonstrated in HT29-MTX cells in response to incubation with supernatant from activated neutrophils. This effect was largely (83%; P < 0.02) inhibited by ICI 200,355, a specific inhibitor of neutrophil elastase. In conclusion, the bacterial peptide fMLP and neutrophil elastase are both potent mucus secretagogues for colon epithelial cells. fMLP also elicits release of the potent neutrophil chemoattractant IL-8 from colon epithelial cells. These findings support the hypothesis that the mucosal inflammation and mucus depletion seen in ulcerative colitis could result from interaction between bacterial peptides and the mucosa.
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Research Article|
September 14 2001
Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis
Keith LEIPER;
Keith LEIPER
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Barry J. CAMPBELL;
Barry J. CAMPBELL
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Michael D. JENKINSON;
Michael D. JENKINSON
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Jeremy MILTON;
Jeremy MILTON
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Lu-Gang YU;
Lu-Gang YU
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Jane DEMOCRATIS;
Jane DEMOCRATIS
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
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Jonathan M. RHODES
1Gastroenterology Research Unit, Department of Medicine, University of Liverpool, Liverpool L69 3GA, U.K.
Correspondence: Professor J. M. Rhodes (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
March 08 2001
Revision Received:
April 30 2001
Accepted:
June 14 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (4): 395–402.
Article history
Received:
March 08 2001
Revision Received:
April 30 2001
Accepted:
June 14 2001
Citation
Keith LEIPER, Barry J. CAMPBELL, Michael D. JENKINSON, Jeremy MILTON, Lu-Gang YU, Jane DEMOCRATIS, Jonathan M. RHODES; Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis. Clin Sci (Lond) 1 October 2001; 101 (4): 395–402. doi: https://doi.org/10.1042/cs1010395
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