1.
Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the
adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the colon. Recent evidence also suggests that the
cyclopentenone prostaglandin (PG) 15-deoxy-delta(12,14)-PGJ(2) (15d- PGJ(2)) functions as an early anti-inflammatory signal. 2. The aim of the present paper is to investigate the effects of 15d-PGJ(2) in rats subjected to experimental
colitis. 3.
Colitis was induced in rats by intra-colonic instillation of
dinitrobenzene sulphonic
acid (
DNBS). 15d-PGJ(2) was administered daily as
intraperitoneal injection (20 or 40 microg kg(-1)). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 4. 15d-PGJ(2) significantly reduced the degree of haemorrhagic diarrhoea and
weight loss caused by administration of
DNBS. 15d-PGJ(2) also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in
myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of
malondialdehyde (MDA) and (iv) of the pro-inflammatory
cytokines tumour
necrosis factor-alpha (
TNF-alpha) and
interleukin-1beta (IL-1beta). 5. Furthermore, 15d-PGJ(2) reduced the increase in immunohistochemical staining for (i)
inducible nitric oxide synthase (iNOS), (ii)
nitrotyrosine and (iii)
poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of
ICAM-1 caused by
DNBS in the colon. 6. Electrophoresis mobility shift assay (EMSA) of inflamed colon revealed that 15d- PGJ(2) also caused a substantial reduction of the activation of
nuclear factor-kappaB (
NF-kappaB). Furthermore, 15d-PGJ(2) stimulates the activation of
heat shock protein 72 (hsp72) in the inflamed colon, as assessed by Western blot analysis. 7. In conclusion, 15d-PGJ(2) reduces the development of experimental
colitis.