Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease

• Published in: Gut 1998-02, Vol.42 (2), p.214-219
• Main Authors: McAlindon, M E, Hawkey, C J, Mahida, Y R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Western; Caspase 1; Cell Biology; Cells, Cultured; Colitis, Ulcerative - immunology; Colitis, Ulcerative - metabolism; Colon - immunology; Colon - metabolism; Crohn Disease - immunology; Crohn Disease - metabolism; Crohn’s disease; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Enzyme Inhibitors - pharmacology; Enzyme-Linked Immunosorbent Assay; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - metabolism; interleukin 1β; interleukin 1β converting enzyme; Interleukin-1 - genetics; Interleukin-1 - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; lipopolysaccharide; Lipopolysaccharides - pharmacology; macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; Medical sciences; Middle Aged; Oligopeptides - pharmacology; Other diseases. Semiology; Polymerase Chain Reaction; RNA, Messenger - analysis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; ulcerative colitis
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.42.2.214

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD). Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa. Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay). Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p