Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometriosis (EM) is characterized by the aberrant growth of endometrial cells at sites outside the uterus. We showed previously that peritoneal leukocyte interleukin-6 (IL-6) production is altered in women with EM relative to that in normal control women. Because studies suggest that IL-6 may be growth regulatory for endometrial cells, we examined IL-6 and IL-6 soluble receptor (IL-6sR) in the peritoneal fluid of 40 women. In addition, the growth responsiveness of ectopic endometrial stromal cells to IL-6 was evaluated. The severity of EM correlated with increased levels of IL-6 accompanied by decreased IL-6sR in peritoneal fluid (controls, 1.0 +/- 0.1 and 525.4 +/- 53; stage I-II EM, 1.4 +/- 0.2 and 274.6 +/- 26; stage III-IV EM, 19.3 +/- 4.6 and 319.4 +/- 26; adhesions, 1.9 +/- 0.4 and 324.7 +/- 26 pmol/L IL-6 and IL-6sR, respectively). Additional studies revealed that unstimulated endometrial stromal cells from ectopic implants secreted this cytokine in vitro. Furthermore, these cells were resistant to growth inhibition induced by exposure to additional IL-6; this response correlated with weak expression of IL-6 receptor. Taken together, these findings lend further support to the hypothesis that dysregulation of IL-6 responses plays a role in the pathophysiology of EM.
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PMID:Dysregulation of interleukin-6 responses in ectopic endometrial stromal cells: correlation with decreased soluble receptor levels in peritoneal fluid of women with endometriosis. 771 20

The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.
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PMID:Aromatase expression in endometriosis. 855 Jul 48

Activated peritoneal macrophages are associated with endometriosis and may play a central role in its aetiology by releasing interleukin-1beta (IL-1beta) in response to refluxed endometrium. Pari passu with the establishment of endometriotic implants is the development of a vascular supply. In this study we investigated the angiogenic properties of two endometrial proteins, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), and assessed their production in response to IL-1beta stimulation in human stromal cells isolated from normal endometrium (NE) and endometriotic lesions (EI). Proliferation of bovine brain capillary endothelial cells (BBCE) with a [(3)H]-thymidine incorporation assay was observed when VEGF (2.1 +/- 0.2-fold; P < 0.05) or VEGF and IL-6 (1.8 +/- 0.1-fold; P < 0.05) were added in vitro, relative to saline-treated control cultures. Northern blot analysis showed induction of VEGF mRNA (2.6-fold; P < 0.05) and IL-6 mRNA (6.3-fold; P < 0.05) transcripts in EI cells, but not NE cells, exposed to IL-1beta. A similar induction was seen with VEGF and IL-6 protein secretion in the responsive EI cells. Reverse transcription-polymerase chain reaction (RT-PCR) for the IL-1 receptor type I (IL-1 RI) indicated that the differential effects of IL-1beta on NE and EI cells was associated with 2.4 +/- 0.1-fold more receptor mRNA in EI versus NE cells. We propose that the ability of IL-1beta to activate an angiogenic phenotype in EI stromal cells but not in NE cells, is mediated by the IL-1 RI.
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PMID:Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1beta. 1069 76

Fertilization and oocyte cleavage rates have previously been demonstrated to be lower for women with endometriosis undergoing IVF compared with controls. This might be related to impaired oocyte function, possibly due to an inflammatory milieu in the pelvis of these women, where an elevated concentration of many cytokines is documented. The aim of this study was to examine whether granulosa cells from women with endometriosis deviated with respect to production of the inflammatory cytokines interleukin-1beta, interleukin-6, interleukin-8 and tumour necrosis factor alpha (TNFalpha) compared with granulosa cells from healthy women, undergoing IVF for male infertility. The effect of human chorionic gonadotrophin on cytokine production was also investigated. Granulosa cells in follicular fluid were obtained at oocyte retrieval for IVF. Incubated cell culture media were analysed by enzyme-linked immunosorbent assay. The basal production of all four cytokines was higher in cells from women with endometriosis when compared to controls, although the increase was only significant for TNFalpha. Chorionic gonadotrophin had no significant effect, although it had a tendency to suppress cytokine release in both patient categories. Whether aberrant cytokine production in granulosa cells from women with endometriosis may disturb fertilizing capacity of oocytes requires study.
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PMID:Elevated expression of tumour necrosis factor alpha in cultured granulosa cells from women with endometriosis. 1083 50

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. We investigated whether SLPI was present in the peritoneal fluid of women with endometriosis and to clarify the role of SLPI in the pathogenesis of endometriosis. Western blot analyses revealed that SLPI protein was detected as a 12 kDa band in peritoneal fluid. The peritoneal fluid concentrations of SLPI, elastase and interleukin-6 were assayed by enzyme-linked immunosorbent assays (ELISA). SLPI concentrations and the SLPI/elastase ratio in the peritoneal fluid of women with endometriosis were higher than in samples from women without endometriosis. There was no significant correlation between concentrations of SLPI and interleukin-6 in the peritoneal fluid. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in peritoneal macrophages, but not lymphocytes. The present findings suggest that SLPI found in the peritoneal fluid of patients with endometriosis may contribute to the pathogenesis of endometriosis.
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PMID:Increased concentrations of secretory leukocyte protease inhibitor in peritoneal fluid of women with endometriosis. 1095 55

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
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PMID:Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis. 1132 93

Based on our previous observation that peritoneal endometriotic (PE) lesions synthesize in vivo substantially more haptoglobin (Hp) than related eutopic tissues, we hypothesized that this increase in Hp production was due to endometrial-peritoneal interactions. As interleukin-6 (IL-6) stimulates Hp in other tissues and is produced by endometrial cells, we tested our hypothesis by evaluating the effects of IL-6 on Hp production by PE cells, normal peritoneal (P) cells, and eutopic endometrial cells from women with (UE-E) and without endometriosis (UE-C) using semiquantitative RT-PCR and enzyme-linked immunoabsorbent assay. Endogenous production of IL-6 was also assessed. Treatment with human recombinant IL-6 and dexamethasone significantly increased Hp production by P or PE cells in a dose- and time-dependent manner (P < 0.05). Hp messenger ribonucleic acid was not detected in UE-E and UE-C cells in the absence or presence of IL-6 and dexamethasone. PE and UE-E cells expressed significantly more IL-6 messenger ribonucleic acid than P and UE-C cells (P < 0.05). Moreover, UE-E cells secreted 6 times more IL-6 protein than UE-C cells (P < 0.05). These findings support our hypothesis and suggest a novel endometrial-peritoneal interaction whereby locally synthesized IL-6 and Hp may participate in the establishment and persistence of peritoneal endometriosis.
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PMID:Interleukin-6 differentially stimulates haptoglobin production by peritoneal and endometriotic cells in vitro: a model for endometrial-peritoneal interaction in endometriosis. 1139 54

Endometriosis, which is common in women of reproductive age, may affect fertility. It is also clear that mechanical disruption of the pelvic anatomy may cause infertility. However, our understanding of the association between the early stage of endometriosis and infertility remains incomplete. Bloody peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis patients and contains various biologically active factors. We found that the concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in PF from patients with endometriosis were significantly higher than that of patients with endometriosis. There were significantly positive correlations between the levels of TNF-alpha and IL-6. We compared the levels of these cytokines with regard to the R-AFS stages and scores, but no differences were observed. In contrast, these cytokines correlate with the number and extent of red color peritoneal endometriosis. TNF-alpha increased the expression of IL-6 messenger RNA and protein in endometriotic stromal cells derived from chocolate cyst in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse preimplantation embryo and impaired sperm function. We concluded that increased levels of IL-6 in peritoneal fluid of patients with active red endometriosis might be related to endometriosis-associated fertility.
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PMID:Role of cytokines in endometriosis-associated infertility. 1183 64

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.
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PMID:Immunological and endocrinological studies on lymphocyte subpopulation and medical treatment for infertility in patients with endometriosis. 1277 Jul 51

Ciliary neurotrophic factor (CNTF) is a gp130 neuroregulatory cytokine belonging to the interleukin-6-type cytokine superfamily. Several lines of evidence suggest that the concentrations of interleukin-6 are elevated in the peritoneal fluid of endometriosis patients. To our knowledge, no study on whether this might also be the case for CNTF levels has been published previously. The CNTF concentrations in the peritoneal fluid were measured by ELISA in 51 women with (n = 31) and without (n = 20) endometriosis. Surgery was scheduled during the proliferative or the secretory phase of the menstrual cycle. CNTF was detectable in the peritoneal fluid of 43% of the women tested. The concentrations of CNTF showed no correlation with the presence of endometriosis or the phase of the menstrual cycle. We found no evidence to suggest that CNTF is involved in the pathogenesis of pelvic endometriosis.
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PMID:Peritoneal fluid concentrations of ciliary neurotrophic factor, a gp130 cytokine, in women with endometriosis. 1289 Sep 30


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