Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells

U. Bocker, A. Damiao, L. Holt, Dong Soo Han, C. Jobin, A. Panja, L. Mayer, R. B. Sartor

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background and Aims: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. Methods: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. Results: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1β. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL- 1Ra I expression in Caco-2 cells decreased IL-1β-stimulated interleukin 8 secretion. Conclusions: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this antiinflammatory cytokine may contribute to mucosal protection.

Original languageEnglish
Pages (from-to)1426-1438
Number of pages13
JournalGastroenterology
Volume115
Issue number6
DOIs
StatePublished - 1998 Jan 1

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Interleukin-1 Receptors
Protein Isoforms
Epithelial Cells
Interleukin 1 Receptor Antagonist Protein
Caco-2 Cells
Inflammation
Interleukin-1
Cell Line
Messenger RNA
Interleukin-1 Type I Receptors
Cytokines
Mucosal Immunity
Tetradecanoylphorbol Acetate
Interleukin-8
Ulcerative Colitis
Population Groups
Crohn Disease
Reverse Transcription
Transfection
Proteins

Cite this

Bocker, U. ; Damiao, A. ; Holt, L. ; Han, Dong Soo ; Jobin, C. ; Panja, A. ; Mayer, L. ; Sartor, R. B. / Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells. In: Gastroenterology. 1998 ; Vol. 115, No. 6. pp. 1426-1438.
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abstract = "Background and Aims: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. Methods: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. Results: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1β. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL- 1Ra I expression in Caco-2 cells decreased IL-1β-stimulated interleukin 8 secretion. Conclusions: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this antiinflammatory cytokine may contribute to mucosal protection.",
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Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells. / Bocker, U.; Damiao, A.; Holt, L.; Han, Dong Soo; Jobin, C.; Panja, A.; Mayer, L.; Sartor, R. B.

In: Gastroenterology, Vol. 115, No. 6, 01.01.1998, p. 1426-1438.

Research output: Contribution to journalArticle

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T1 - Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells

AU - Bocker, U.

AU - Damiao, A.

AU - Holt, L.

AU - Han, Dong Soo

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AU - Panja, A.

AU - Mayer, L.

AU - Sartor, R. B.

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N2 - Background and Aims: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. Methods: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. Results: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1β. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL- 1Ra I expression in Caco-2 cells decreased IL-1β-stimulated interleukin 8 secretion. Conclusions: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this antiinflammatory cytokine may contribute to mucosal protection.

AB - Background and Aims: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. Methods: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. Results: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1β. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL- 1Ra I expression in Caco-2 cells decreased IL-1β-stimulated interleukin 8 secretion. Conclusions: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this antiinflammatory cytokine may contribute to mucosal protection.

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