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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
Authors:Gregory M S  Duffner L A  Hahn E L  Tai H H  Faunce D E  Kovacs E J
Institution:Department of Cell Biology, Neurobiology, and Anatomy, Burn and Shock Institute, Maywood, Illinois 60153, USA.
Abstract: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).
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