Expression of interleukin 1 beta and interleukin 1 beta converting enzyme by intestinal macrophages in health and inflammatory bowel disease.
BACKGROUND
In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1 beta (IL-1 beta, 31 kD) is processed by IL-1 beta converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1 beta is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD).


OBJECTIVE
To investigate the expression and processing of IL-1 beta 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-1 beta 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-1 beta 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 < 0.01).


CONCLUSIONS
Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1 beta, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1 beta in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.
McAlindon
M E
ME
Division of Gastroenterology, School of Medical and Surgical Sciences, University Hospital, Queen's Medical Centre, Nottingham, UK.
Hawkey
C J
CJ
Mahida
Y R
YR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D020170:Caspase 1; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009842:Oligopeptides; D012333:RNA, Messenger; C096429:L 709049; D003546:Cysteine Endopeptidases; D020170:Caspase 1