IL-1β increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells.

Abstract

Immune tolerance to endometriotic cells is important to promote endometriosis. Tryptophan 2,3-dioxygenase (TDO) enhances immune tolerance by catabolizing tryptophan to kynurenine. We studied whether interleukin-1β (IL-1β), a typical endometriosis-associated cytokine, affects the expression of TDO and the catabolism of tryptophan in endometrioma stromal cells (ESCs). We also studied whether the expression of TDO is involved in IL-1β-induced secretion of IL-6 and IL-8 in ESCs. Nineteen endometriotic patients of reproductive age with normal menstrual cycles were recruited. Primary cultures of ESCs were treated with IL-1β and TDO siRNA. TDO mRNA was measured using quantitative PCR. TDO protein was measured using Western blotting. Concentrations of kynurenine in condition media were measured using Ehrlich reagent. Concentrations of tryptophan in conditioned media were measured using tryptophan detection kit. Concentrations of IL-6 and IL-8 in conditioned media were measured using ELISA kits. IL-1β (1 ng/mL) increased the expression of TDO mRNA and TDO protein in ESCs. IL-1β-treated ESCs increased the production of kynurenine and the effect was inhibited by TDO siRNA. Treatment with the siRNA also decreased IL-1β-induced secretion of IL-6 and IL-8 from ESCs. IL-1β is suggested to stimulate tryptophan catabolism and production of IL-6 and IL-8 by increasing TDO expression in endometriosis.