Regulatory roles of PGE2 in LPS-induced tissue damage in bovine endometrial explants

Regulatory roles of PGE2 in LPS-induced tissue damage in bovine endometrial explants
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PGE2 在 LPS 诱导的牛子宫内膜外植体组织损伤中的调节作用

DOI:
10.1016/j.ejphar.2019.03.044
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发表时间:
2019-06-05
影响因子:
5
通讯作者:
Cao, Jinshan
Cao, Jinshan
中科院分区:
医学2区
文献类型:
--
作者:
Deng, Yang;Liu, Bo;Cao, Jinshan

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Bovine endometritis is the most common uterine disease following parturition. The role of prostaglandin E-2 (PGE(2)) in regulating normal physiological function in the bovine endometrium has been clearly established. Although PGE(2) accumulation is observed in multiple inflammatory diseases, such as endometritis, its association with pathogen-induced inflammatory damage in the endometrium is unclear. To clarify the role of PGE(2) in lipopolysaccharide (LPS)-induced endometritis in cultured bovine endometrial explants, the levels of PGE(2) secretion, prostaglandin synthetases, pro-inflammatory factors, and damage-associated molecular patterns (DAMPs) were evaluated in the present study. Significant PGE(2) accumulation in response to LPS stimulation, upregulation of prostaglandin-endoperoxide synthase-2 (PTGS-2), microsomal prostaglandin E synthase-1 (mPGES-1), pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), and induced nitric oxide synthase (iNOS)/nitric oxide (NO) and DAMPs including hyaluronan binding protein 1 (HABP1) and high mobility group box-1 (HMGB1), were observed compared to the control group. LPS induced distinct damage in the bovine endometrium, characterized by morphological changes and increases in HABP1 and HMGB1 expression. PTGS-2 inhibitors CAY10404 and NS398 effectively decreased the secretion of PGE(2) and the expression of prostaglandin synthetases, pro-inflammatory factors and DAMPs, and alleviated LPS-induced tissue damage. These results indicate that PGE(2) accumulates via PTGS-2 and mPGES-1 and induces tissue damage by upregulating pro-inflammatory factors and DAMPs in LPS-treated bovine endometrial explants. These findings provide a basis for the effect of PGE(2) on LPS-treated bovine endometrium, and suggest a potential target for curing endometritis.