Peroxisome proliferating activating receptor gamma–independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

Capsule:
Thiazolidinediones reduce the concentration of inflammatory cytokines IL-6 and IL-8 secreted from primary cultured endometrial stromal cells through a PPARg–independent mechanism.

Authors:
Brett McKinnon, Ph.D., Nick A. Bersinger, Ph.D., Michael D. Mueller, M.D.
Volume 97, Issue 3 , Pages 657-664, March 2012

Objective:
To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.

Design:
In vitro study using eutopic endometrial tissue.

Setting:
University hospital.

Patient(s):
Premenopausal women undergoing laparoscopy for infertility or abdominal pain.

Intervention(s):
Isolation of endometrial stromal cells and the culture of these cells in the presence of thiazolidinediones, ciglitazone and pioglitazone, both with and without a pretreatment of the specific, irreversible PPAR-γ antagonist GW9662.

Main Outcome Measure(s):
Quantitation of interleukin (IL)-6 and IL-8 released into the cell culture medium by ELISA. Real-time polymerase chain reaction to quantitate PPAR-γ gene expression in the primary cell preparations and the expression of IL-6 and IL-8 after thiazolidinedione treatment.

Result(s):
Treatment of stromal cells with thiazolidinediones attenuated IL-6 and IL-8 release in a dose-dependent manner. This effect was not inhibited by GW9662 pretreatment. Ciglitazone induced IL-6 messenger RNA expression, an effect that was suppressed by GW9662 pretreatment.

Conclusion(s):
Thiazolidinediones decrease the proinflammatory cytokines IL-6 and IL-8 in endometrial stromal cells via a PPAR-γ–independent mechanism. A better understanding of the anti-inflammatory action of this class of drugs may improve their safety and efficacy for endometriosis treatment.

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