Differential production of prostaglandin E(2) in male and female mice subjected to thermal injury contributes to the gender difference in immune function: possible role for 15-hydroxyprostaglandin dehydrogenase.
We have previously reported a macrophage-mediated gender difference in postburn immunosuppression, which was dependent upon elevated levels of circulating 17beta-estradiol (E(2)) and, in part, interleukin-6. Herein we examined the role of prostaglandin E(2) (PGE(2)), a potent suppressor of cell-mediated immunity. Circulating levels of PGE(2) were significantly elevated in females but not males at 10 days postburn (P < 0.01), and indomethacin treatment fully restored the delayed-type hypersensitivity and splenocyte proliferative responses of thermally injured females. While there was no difference in cyclooxygenase-2 protein expression in the lungs and liver of thermally injured male and female mice, there was a marked decrease in the protein expression of 15-hydroxyprostaglandin dehydrogenase in females. These data demonstrate that PGE(2) is a critical mediator of immunosuppression in thermally injured female mice and that the increase in circulating PGE(2) is derived, in part, from decreased degradation and clearance of PGE(2).
Gregory
M S
MS
Department of Cell Biology, Neurobiology, and Anatomy, Burn and Shock Institute, Maywood, Illinois 60153, USA.
Duffner
L A
LA
Hahn
E L
EL
Tai
H H
HH
Faunce
D E
DE
Kovacs
E J
EJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002056:Burns / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000008:administration & dosage / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007509:Irritants; D007527:Isoenzymes; D004139:Dinitrofluorobenzene; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin