Effects of adrenomedullin on the expression of inflammatory cytokines and chemokines in oviducts from women with tubal ectopic pregnancy: an in-vitro experimental study

Abstract

BackgroundThe occurrence of tubal ectopic pregnancy (tEP) is related to the inflammation of the oviduct. Recently, Adrenomedullin (ADM) was found highly expression in human oviduct. The current study is to investigate whether ADM have a modulatory action on inflammatory cytokines and chemokines in oviductal tissue from women with tubal ectopic pregnancy (tEP).MethodsOviductal isthmus samples were collected from women with tEP undergoing salpingectomy, and women undergoing hysterectomy for benign gynaecological conditions. The mRNA and protein levels of inflammatory cytokines/chemokines were assayed by PCR (n = 6 for tEP, n = 5 for controls) and protein microarray methods (n = 5 for both tEP and controls) respectively.ResultsSome of the inflammatory cytokines/chemokines were upregulated by ADM in oviducts from tEP patients at both mRNA and protein levels. Incubation of oviduct from tEP patients with ADM for 24 h down-regulated some of these cytokines/chemokines.ConclusionOur results suggest an additional mechanism whereby ADM insufficiency may increase the susceptibility to tEP through diminished anti-inflammatory activity. The actual impact of the relationship between ADM and inflammatory process on tubal implantation needs further exploration.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0117-x) contains supplementary material, which is available to authorized users.

Adrenomedullin RegulatesIL-1βGene Expression in F4/80+ Macrophages during Synovial Inflammation

“…Several recent studies have provided evidence that AM has anti-inflammatory effects by regulating innate immunity responses, including the reduced production of proinflammatory cytokines, including TNF-alpha, IL-6, and IL-1 [ 14 , 15 , 29 , 30 ]. For example, AM suppresses the in vitro secretion and gene transcription of TNF- α and IL-6 in the murine monocyte/macrophage cell line RAW 264.7 [ 14 ] and also attenuates TNF- α and IL-1 β production in an in vivo acute lung injury mouse model [ 15 ].…”

Alteration of the immune cell profiles in the pathophysiology of tubal ectopic pregnancy

“…Some of the view are the local Mφ tend to differentiate into M1 phenotype, since tubal infection is the chief risk factor of TEP which involves in exacerbating pro‐inflammatory reactions in the fallopian tubes . Moreover, the tube tissues of women with TEP produce higher levels of pro‐inflammatory factors such as GM‐CSF, IFN‐γ, and IL‐2 into the surrounding environment than of non‐pregnant women, creating a pro‐inflammatory microenvironment in the fallopian tube. However, others maintain that tubal Mφ of TEP is M2 phenotype, since the local implantation requires an immunosuppressive environment to support conceptus which favors the differentiation of monocytes toward M2 phenotype .…”

“…In 35%‐50% of the patients with EP, pelvic inflammatory disease (PID) is thought to be the main predisposing condition . Serum levels of various inflammatory cytokines and chemokines such as interleukin (IL)‐1β, IL‐6, IL‐8, interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF) are higher in women with EP than in women with normal eutopic pregnancy . The fallopian tube tissue of TEP also expresses higher levels of pro‐inflammatory factors such as IL‐1, IL‐6, and IL‐8 .…”

Repeated Ectopic Pregnancy after Unilateral or Bilateral Salpingectomy in Assisted Reproductive Technology

“…Recently, some studies reveal that abnormal endometrial gene expression and cytokines secretion, as well as aberrant uterine receptivity are contributing to the pathogenesis of ectopic pregnancy [16,17]. The embryos can only implant into the endometrium where it is in the implantation window.…”