Interleukin I (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-la and (3 mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-la was significantly elevated at 4 h (9.4±1.5 ng/g colon), progressively increased at 48 h (31±5.8 ng/g) and then decreased by 96 h (11.5±3.4 ng/g). IL-lft levels were 2.0±0.5 ng/g colon at 4 h, 5.0±1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-la levels were highly correlated with inflammation (r = 0.885, P < 0.0001), edema (r = 0.789, P < 0.0001) and necrosis (r = 0.752, P < 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-Ira) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2±0.4 to 1.4±0.3, P < 0.02), edema (from 2.2±0.4 to 0.6±0.3, P < 0.01) and necrosis (from 43±10% to 6.6±3.2%, P < 0.03) compared to vehicle-matched colitis animals. These studies demonstrate
Background and aim-Epidermal growth factor (EGF) and transforming growth factor (TGF-), members of the EGF family of growth factors, protect rat gastric and colonic mucosa against injury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was to evaluate the endogenously expressed ligand mediating the protective eVect of EGF/TGF-in vivo. Methods-In an experimental model of trinitrobenzene sulphonic acid (TNBS)/ ethanol induced colitis in rats EGF and TGF-expression was evaluated using a ribonuclease protection assay, northern blot analysis, western blot analysis, and immunohistochemistry.
Results-TGF-mRNA increased 3-4 times at 4-8 hours after induction of colitis and returned to control levels within 24 hours. TGF-immunoreactive protein with a molecular size of about 28 kDa representing TGF-precursors increased markedly after induction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the rat colon and no EGF protein was observed by immunohistochemistry or western blot analysis. Conclusions-TGF-precursors are the main ligands for the EGF receptor in acute colitis. It is hypothesised that TGFprecursors convey the biological activity of endogenous TGF-peptides during mucosal defence and repair.
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