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High mobility group box-1 and Toll like receptor 4 in Endometriosis: Mediating NF-kB pathway
( Bo Hyon1 ),( Yun Ji Jung ),( Seung Joo Chon ),( Yoo Jin Lee ),( E Jung Han ),( Sihyun Cho ),( Young Sik Choi ),( Byung Seok Lee ),( Seok Kyo Seo ) 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-
목적: The aim of the study was to examine the sterile, chronic inflammatory status in endometriosis by detecting High mobility group box-1 (HMGB-1), and HMGB-1 signaling through toll like receptor (TLR) 4 in endometrial stromal cell, which activates NF-kB pathway that might play a pathogenic role in endometriosis. 방법: Total 69 patients who had undergone hysterectomy from March, 2012 to March, 2014 were included: 39 patients who had endometriosis as case group, 30 participants without endometriosis as the control. Expression of HMGB-1 in endometrium was examined by immunohistochemistry. From endometriosis patient, eutopic endometrium was obtained and used to culture in vitro. To confirm the association of HMGB-1 and TLR4 in NF-kB pathway, the cultured human endometrial stromal cells (HESCs) were treated with recombinant HMGB-1 (15 ng/mL) for 0, 12, 24, 48 hrs. TLR4 antagonist (LPS-RS) was added after rHMGB-1 treatment to HESCs to see the change of proliferation after inhibiting TLR4. CCK8 proliferation assay kit. Real-time PCR and western blotting were used to examine the proliferation, quantification of the mRNA and protein. Specific inhibitor of NF-κB signaling pathway (TPCA-1) was used to explore the role of NF-κB signaling pathway in HESCs proliferation. 결과: HMGB-1 expression was significantly higher in glandular epithelial and stromal cells of endometriosis group compared to the controls. rHMGB-1 significantly enhanced cell proliferation in HESCs and increased TLR4 expression by dose dependent fashion. Inhibiting TLR4 by LPS-RS, cell proliferation in HESCs and expression of TLR4 were significantly decreased comparing to the controls. After blocking NF-kB pathway with TPCA-1, cell proliferation in HESCs was significantly decreased by dose dependent fashion. 결론: This study showed that HMGB-1 may play an important role through TLR4 and NF-kB pathway, in inflammatory cascade of pathogenesis in endometriosis.