Estimation of mucosal inflammatory mediators in rat DSS-induced colitis. Possible role of PGE(2) in protection against mucosal damage.
In order to investigate the mucosal injury mechanism in UC, we made dextran sulfate sodium (DSS)-induced colitis in rat and examined pathological findings, MPO activity, PGE(2) level, and local mRNA expression and secretion of IL-1 beta, TNF-alpha, GRO/CINC-1 and IL-10 in DSS colitis mucosa. Moreover, we estimated the correlation between the severity of mucosal damage and changes of these local inflammatory mediators' values. Neutrophil infiltration was marked and MPO activity was locally increased in proportion to the severity of mucosal damage. The mRNA expression and secretion of IL-1 beta, GRO/CINC-1 and IL-10 were increased. Especially, the secretions of IL-1 beta and GRO/CINC-1 were increased in proportion to the severity of mucosal damage. However, those of TNF-alpha were not increased in the colitis mucosa. An abnormal macrophage function and the presence of macrophage subtypes producing different cytokines would be predicted from our TNF-alpha data. The lesion was less severe in the colonic mucosa with higher levels of endogenous PGE(2), while it was more severe in the colonic mucosa with lower levels of endogenous PGE(2), implicating this compound as an inhibitory factor against the development of inflammation in the affected mucosa. Our results suggest that PGE(2) might have therapeutic applicability to UC.
Hirata
I
I
Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan.
Murano
M
M
Nitta
M
M
Sasaki
S
S
Toshina
K
K
Maemura
K
K
Katsu
K
K
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D003092:Colitis / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D016264:Dextran Sulfate / Q000008:administration & dosage; D015232:Dinoprostone / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
D000925:Anticoagulants; D016207:Cytokines; D012333:RNA, Messenger; D016264:Dextran Sulfate; D009195:Peroxidase; D015232:Dinoprostone