The expression of interleukin (IL)-6, IL-8, and their receptors in fallopian tubes with ectopic tubal gestation

Balasubramaniam, Erin S.; Noorden, Susan Van; El‐Bahrawy, Mona

doi:10.1016/j.fertnstert.2012.06.004

Cited by 29 publications

(38 citation statements)

References 38 publications

(60 reference statements)

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“…The levels of IL-1␤, IL-4, IL-5, IL-6, and IL-10 were reported to be significantly higher in enriched cervical T cells stimulated with chlamydial inclusion (Inc) membrane proteins from women with C. trachomatis-related infertility (n ϭ 18) than in those from C. trachomatis-positive fertile women (n ϭ 14) (53). While ectopic pregnancy is not only a Chlamydia-related pathology, a study by Balasubramaniam et al that found that levels of the cytokines IL-8 and IL-6 were significantly upregulated in the fallopian tubes immediately at the location of implantation of ectopic pregnancy but not in the fallopian tubes of women undergoing benign hysterectomy (54). A very recent study found that differences in IFN-␥ levels correlated with differences in the chlamydial cellular morphologies at the cervix when comparing two patients (55).…”

Section: Immune Responses From Reproductive Sites and Tissuesmentioning

confidence: 99%

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

et al. 2015

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SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.

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Section: Immune Responses From Reproductive Sites and Tissuesmentioning

confidence: 99%

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

et al. 2015

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“…In addition, IL8 has a pro-inflammatory role in the fallopian tube during tubal infections and subsequent hydrosalpinges (accumulation of inflammatory fluid within the lumen) (Balasubramaniam et al, 2012). Many of these changes in signaling molecules and hormones facilitate proper fertilization and embryo development in the fallopian tube and can serve as surrogate measurements of normal fallopian tube function (Carlsson et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

Zhu

Rashedi

et al. 2016

Mol. Hum. Reprod.

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STUDY QUESTION: Do interactions between human fallopian tube epithelium and murine follicles occur during an artificial reproductive cycle in a co-culture system in vitro?SUMMARY ANSWER: In a co-culture system, human fallopian tissues responded to the menstrual cycle mimetic by changes in morphology and levels of secreted factors, and increasing murine corpus luteum progesterone secretion.WHAT IS KNOWN ALREADY: The entire fallopian tube epithelium, including ciliated and secretory cells, can be regulated in the reproductive cycle. Currently, there are no in vitro culture models that can monitor fallopian tissues in real time in response to factors produced by the ovary. In addition, there are no reports on the impact of fallopian tissue on ovarian function during the menstrual cycle.STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Human fallopian tissue (n = 24) was obtained by routine hysterectomies from women (aged 26-50 years, mean age = 43.6) who had not undergone exogenous hormonal treatment for at least 3 months prior to surgery. CD1 female mice were used for ovarian follicle isolation. The human fallopian epithelium layers were either co-cultured with five murine multilayer secondary follicles (150-180 μm follicles, encapsulated in one alginate gel bead) for 15 days or received stepwise steroid hormone additions for 13 days. The fallopian tissue morphology and cilia beating rate, as measured by an Andor Spinning Disk Confocal, were investigated. Oviduct-specific glycoprotein 1 (OVGP1), human insulin-like growth factor 1 (hIGF1), vascular endothelial growth factor A (VEGF-A) and interleukin 8 (IL8) as biological functional markers were measured either by ELISA or western blot to indicate dynamic changes in the fallopian epithelium during the reproductive cycle generated by mouse follicles or by stepwise steroid hormone induction. Three or four patients in each experiment were recruited for replicates. Data were presented as mean ± SD and further analyzed using one-way ANOVA followed by Tukey's multiple comparisons test. MAIN RESULTS AND THE ROLE OF CHANCE:The cultured fallopian tube epithelium responded to exogenous steroid hormone stimulation, as demonstrated by enhanced cilia beating rate (~25% increase, P = 0.04) and an increase in OVGP1 secretion (P = 0.02) in response to 1 nM estradiol (E 2 ) treatment when compared with 0.1 nM E 2 . Conversely, 10 nM progesterone plus 1 nM E 2 suppressed cilia beating rate by~30% (P = 0.008), while OVGP1 secretion was suppressed by 0.1 nM E 2 plus 50 nM progesterone (P = 0.002 versus 1 nM E 2 alone). Human fallopian tube epithelium was co-cultured with murine secondary follicles to mimic the human menstrual cycle. OVGP1 and VEGF-A secretion from fallopian tissue was similar with stepwise hormone treatment and when cultured with murine follicles. However, the secretion patterns of hIGF1 and IL8 differed in the luteal phase when comparing steroid treatment with follicle co-culture. In co-culture, hIGF1 secretion was suppressed in the luteal versus follicular phase (P = 0.005)...

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“…Although PID and/or a history of sexually transmitted infection are major risk factors for EP [37,40], none of the earlier studies correlated their findings with possible tubal infection [5,49]. The present study measured the prevalence of tubal infection with CMV and a significant increase in the frequency of positive cases by PCR was observed in specimens obtained from EP (22.9 %) compared with control (8.2 %) and it was associated with 3 times greater risk of developing EP.…”

Section: Discussionmentioning

confidence: 95%

“…IL-6 and its signalling molecules are all synthesised by the human Fallopian tube [14,45,48]. IL-6, which inhibits tubal ciliary beats in vitro [32], has been also shown by immunohistochemistry only with an increase in tubal samples collected from EP and the highest expression was detected in tissues adjacent to the implantation site [5]. However, the authors failed to detect significant alterations in the protein expression of IL6Ra receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, abnormal expression of IL-6 by the endometrium has been associated with implantation failure, abortion and poor reproductive outcomes [13,20]. Nevertheless, the available studies on the role of the IL-6 in the pathophysiology of EP are few and the results are conflicting [5,49]. Additionally, none of the previous studies measured the effect of a tubal infection on the production of IL-6 by Fallopian tubal tissues.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant expression of interleukin-6 and its receptor in Fallopian tubes bearing an ectopic pregnancy with and without tubal cytomegalovirus infection

Ashshi

2016

VirusDis.

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Cytomegalovirus (CMV) has recently been suggested as a potential risk factor for the development of ectopic pregnancy (EP) following upper genital tract infection in women. However, little is known about its associated underlying pathogenic mechanisms. This was a prospective case-control study that measured the prevalence of CMV infection in Fallopian tubes (FT) bearing an EP and its effects on the tubal expression of interleukin (IL)-6 and its signaling molecules, which are known to play significant roles in the immune response against CMV infection as well as embryo implantation. Fresh FTs from 96 EPs during salpingectomy and another 61 women at the midluteal phase during total abdominal hysterectomy (TAH) were collected to measure the rate of CMV by an IVD CE PCR kit. The participants were then classified to measure the expression of IL-6, its receptor (IL6R) and intracellular mediators (gp-130, STAT3) by immunohistochemistry and quantitative RT-PCR. The results showed significantly higher (P = 0.01) rates of CMV in FTs obtained from EP (22.9 %) compared with controls (8.2 %). IL-6 (P = 0.003), IL6Ra (P = 0.02), gp 130 (P = 0.008) and STAT3 (P = 0.03) were significantly higher in TAH-positive (n = 5) compared with TAHnegative FTs by immunohistochemistry. Furthermore, the expression in the non-infected EP samples was significantly higher for IL-6 (P = 0.004), IL6R (P = 0.007), gp130 (P = 0.006) and STAT3 (P = 0.007) compared with negative TAH. Similar results were observed by quantitative PCR. CMV-positive EP samples showed the highest significant increase of the studied molecules by all techniques. In conclusion, Fallopian tubal infection with CMV is higher in EP and could predispose to embryo implantation by up-regulating the expression of IL-6 and its related molecules as part of tubal innate immune response. Further in vitro and in vivo studies are compulsory to illustrate the roles of IL-6 and CMV in the pathogenesis of EP.

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The expression of interleukin (IL)-6, IL-8, and their receptors in fallopian tubes with ectopic tubal gestation

Cited by 29 publications

References 38 publications

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

Human fallopian tube epithelium co-culture with murine ovarian follicles reveals crosstalk in the reproductive cycle

Aberrant expression of interleukin-6 and its receptor in Fallopian tubes bearing an ectopic pregnancy with and without tubal cytomegalovirus infection

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