Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats.
A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A2 (detected as thromboxane B2) and prostaglandin I2 (detected as 6-ketoprostaglandin F1alpha). Thromboxane B2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F1alpha level exceeded that of thromboxane B2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1alpha and -1beta detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1alpha into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-ketoprostaglandin F1alpha resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1alpha injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1alpha.
Tonai
T
T
Department of Orthopedic Surgery and Clinical Research Institute, National Zentsuji Hospital, Kagawa, Japan.
Taketani
Y
Y
Ueda
N
N
Nishisho
T
T
Ohmoto
Y
Y
Sakata
Y
Y
Muraguchi
M
M
Wada
K
K
Yamamoto
S
S
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008565:Membrane Proteins; D010544:Peroxidases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology*; D013931:Thromboxanes / Q000096:biosynthesis / Q000378:metabolism
D005938:Glucocorticoids; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D013931:Thromboxanes; D003907:Dexamethasone; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat