Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice.
OBJECTIVE
Chronic abdominal symptoms develop in some patients after acute enteric infection. This study examined mechanisms underlying smooth muscle hypercontractility that persists after acute infection in mice.


METHODS
Euthymic and athymic National Institutes of Health (NIH) Swiss mice were infected with Trichinella spiralis and studied 4 weeks postinfection (PI). Isometric tension was assessed in longitudinal muscle. Cytokine and cyclooxygenase (COX)-2 messenger RNA was determined in the muscularis externa by reverse-transcription polymerase chain reaction. COX-2 protein was identified by immunohistochemistry and prostaglandin E(2) was measured by enzymatic immunoassay. Studies were performed in euthymic and athymic NIH Swiss mice 28 days PI and in the presence or absence of treatment with corticosteroid or COX inhibitors.


RESULTS
Muscle hypercontractility was evident in euthymic mice but was attenuated in athymic mice or in steroid-treated euthymic mice 28 days PI. Expression of Th2 cytokines interleukins 4, 5, and 13 was increased during the acute infection but not thereafter. COX-2 was localized to muscle and its enzymatic activity remained significantly increased in the muscle on day 28 PI. Selective COX-2 inhibition in vitro reduced the sustained increase in tension generation.


CONCLUSIONS
These findings show that COX-2 activation in resident cells of the muscularis externa contributes to the muscle hypercontractility that persists after infection.
Barbara
G
G
Intestinal Disease Research Program and Division of Gastroenterology, Health Sciences Center, McMaster University, Hamilton, Ontario, Canada.
De Giorgio
R
R
Deng
Y
Y
Vallance
B
B
Blennerhassett
P
P
Collins
S M
SM
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D003109:Colonic Diseases, Functional / Q000209:etiology*; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics; D015232:Dinoprostone / Q000032:analysis; D007422:Intestines / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000150:complications*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007527:Isoenzymes; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone