Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture

Abstract

The relationship between the immune and the endometrial systems has been recently suggested to be critical to the development of endometriosis. We previously showed that one of the molecules involved in the complex events that allow this interaction is the adhesion molecule intercellular adhesion molecule (ICAM)-1. This study was designed to evaluate whether differences in ICAM-1 mRNA and protein expression might exist between eutopic endometrial cells and ectopic cells derived from endometriomas. Stromal cells were dispersed from samples of endometrium and ovarian endometriomas biopsied synchronously from 24 patients with endometriosis. We established that the relative expression of ICAM transcript was significantly higher in ectopic cells than that found in cultures derived from endometrial samples. Moreover, ectopic cells demonstrated a significant overexpression of ICAM-1 protein in both its cell-bound and soluble form (sICAM-1) (P < 0.05). Interestingly, endometrial secretion of sICAM-1 was shown to vary during the menstrual cycle as proliferative phase samples released significantly higher concentrations of the soluble protein compared to the secretory phase. In contrast, this cycle-dependent pattern was absent in stromal cells derived from endometriomas. Moreover, interleukin (IL-1beta) was able to increase sICAM-1 shedding from endometrial cells in a concentration-dependent manner and this IL-1beta-mediated induction could be slightly enhanced by oestradiol. As sICAM-1 is able to interfere with ICAM-1-mediated immune functions, the release of higher concentrations from ectopic samples may be the mechanism by which ectopic endometrial cells escape immunosurveillance.

Association and Interaction of Polymorphisms in Angiogenesis Genes Involved in Endometriosis.

“…Price et al showed that the -1306C/T cause strikingly low promoter activity, because it disrupts a Sp1-binding site (CCACC box). Because Sp1 is a ubiquitously expressed transcriptional factor that regulates a variety of gene in a constitutive or inducible manner (13,(26)(27)(28), it is clear that sequence variations may alter the level and specificity of gene transcription Accumulated evidence has shown that the C/T transition at this site could lead to lower levels of MMP-2 protein in individuals carrying the T/T genotype than in those carry the C/C or C/T genotype. Our results indicate that the "T"-allele is associated (OR is 1.5098 (95% CI=1.0218-2.309)) with women suffering with endometriosis Previous functional studies using promoter-reporter assays indicated a, 50% higher promoter activity of "T" allele compared to "C" allele (23).…”

“…ICAM-1 G241A polymorphism has been studied in Italian and Japanese women with endometriosis (13,15). The latter showed an association of "A" allele with endometriosis, while no association of this polymorphism was found in Japanese women.…”

“…Polymorphisms in the three candidate genes MMP-9, MMP-2 & ICAM-1 are considered to be important for the variation seen in polygenic disorders like endometriosis (9,10) where angiogenesis plays an integral part in the growth and establishment of endometriotic lesions. Hence we decided to study the single nucleotide polymorphisms in these three genes which participate in angiogenesis (11,12,13) in MMP-2 (-C1306T), MMP-9 (-C 1562 T) and ICAM-1 (G241A).…”

“…Hence we decided to study the single nucleotide polymorphisms in these three genes which participate in angiogenesis (11,12,13) in MMP-2 (-C1306T), MMP-9 (-C 1562 T) and ICAM-1 (G241A). All these SNPs have been evaluated in different ethinic groups (14,15, …”

Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM-1 in TNF-α-activated human endometrial stromal cells

“…ICAM-1 is expressed in cultured human endometrial stromal cells (HESCs), as well as in endometrial stromal cells in the human endometrium in situ (7,8). Furthermore, in patients with endometriosis, ICAM-1 is more strongly expressed in ectopic endometrial stromal cells than in eutopic endometrial stromal cells (9), and the elevated expression of ICAM-1 is induced in endometrial stromal cells by pro-inflammatory cytokines, such as IFN-γ (10). These data suggest that crosstalk may occur between endometrial stromal cells and leukocytes in the endometrium and peritoneal fluid via ICAM-1 and its receptors, contributing to the pathological processes of endometriosis.…”