Bioactive IL-18 expression is up-regulated in Crohn's disease.
An imbalance of immunoregulatory factors is believed to contribute to uncontrolled mucosal Th1 cell activation in Crohn's disease (CD). IL-18, a macrophage-like cell-derived cytokine, is involved in Th1 clone development, and IFN-gamma production. Therefore, IL-18 expression was investigated in CD. Whole mucosal intestinal tissue and lamina propria mononuclear cells (LPMC) of 12 CD and 9 ulcerative colitis (UC) patients and 15 non-inflammatory bowel disease (IBD) controls were tested for IL-18 by semiquantitative RT-PCR and Western blot analysis. Transcripts for IL-18 were found in all samples tested. However, increased IL-18 mRNA accumulation was detected in both mucosal and LPMC samples from CD in comparison to UC and controls. In CD, transcripts for IL-18 were more abundant in the mucosal samples taken from involved areas. An 18-kDa band consistent with mature IL-18 was predominantly found in CD mucosal samples. In mucosal samples from non-IBD controls, IL-18 was present as a 24-kDa polypeptide. Consistently, active IL-1beta-converting enzyme (ICE) subunit (p20) was expressed in samples from either CD or UC, whereas, in colonic mucosa from non-IBD controls, ICE was synthesized as precursor (p45) only. To confirm that IL-18 produced in CD tissue was functionally active, CD LPMC were treated with a specific IL-18 antisense oligonucleotide. In these cultures, IL-18 down-regulation was accompanied by a decrease in IFN-gamma expression. In aggregate, our data indicate that IL-18 up-regulation is a feature of CD and suggest that IL-18 may contribute to the local immunoinflammatory response in CD.
Monteleone
G
G
Dipartimento di Medicina Sperimentale, Universita' di Catanzaro, Catanzaro, Italy.
Trapasso
F
F
Parrello
T
T
Biancone
L
L
Stella
A
A
Iuliano
R
R
Luzza
F
F
Fusco
A
A
Pallone
F
F
D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology*
D020382:Interleukin-18; D012333:RNA, Messenger; D020170:Caspase 1