Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis

Context: Endometriosis is an estrogen-dependent, chronic inflammatory disease. Recent studies have shown that vitamin D (VD) is an effective modulator of the immune system and plays an important role in controlling many inflammatory diseases. Objective: The objective of the study was to clarify the in vitro effects of 1,25-dihydroxy vitamin D-3 (1,25[OH](2)D-3) on human endometriotic stromal cells (ESCs) and to determine the serum levels of VD in endometriosis patients. Design, Patients, and Main Outcome Measures: ESCs were isolated from ovarian endometrioma and cultured with 1,25(OH)(2)D-3. Gene expression of IL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine incorporation assay. Apoptosis was assessed using flow cytometry. The expression of inhibitory-kappa B alpha protein was detected using Western blotting. The serum levels of 25-hydroxyvitamin D-3 and 1,25(OH)(2)D-3 were measured by a RIA. Results: In vitro studies showed that 1,25(OH)(2)D-3 significantly reduced IL-1 beta- or TNF-alpha- induced inflammatory responses, such as IL-8 expression and prostaglandin activity. 1,25(OH)(2)D-3 also reduced viable ESC numbers and DNA synthesis but did not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)(2)D-3. 1,25(OH)(2)D-3 inhibited nuclear factor-kappa B activation. The serum 25-hydroxyvitamin D-3 levels were significantly lower in women with severe endometriosis than in the controls and women with mild endometriosis. Serum 1,25(OH)(2)D-3 levels were not different between groups. Conclusions: VD modulates inflammation and proliferation in endometriotic cells, and a lower VD status is associated with endometriosis. Taken together, VD supplementation could be a novel therapeutic strategy for managing endometriosis.