New insights into pattern recognition receptors and their ligands in gynecologic pathologies

Yamada, Yoshihiko; Shinmoto, Hiroshi; Onogi, Akira; Shoji, Hirokazu; Kawaguchi, Ryuji; Yoshida, Shozo; Furukawa, Naoto; Nagai, Akiko; Tanase, Yasuhito; Tsunemi, Taihei; Oi, Hidekazu; Kobayashi, Hiroshi

doi:10.1016/j.humimm.2010.12.009

Cited by 10 publications

(3 citation statements)

References 81 publications

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“…We previously reported that mRNAs encoding TLRs-1, -2, -4, -5, -6, and -9 and NODs-1 and -2 were expressed in both endometriosis and non-endometriosis benign diseases, with the levels of expression of TLR-2 and -9 and NOD-1 and -2 mRNAs being significantly higher in patients with than without endometriosis. These findings suggest that innate immune activity is increased in the abdominal cavity of patients with endometriosis, and therefore may be involved in the pathophysiology of endometriosis 10 - 12 .…”

Section: Discussionmentioning

confidence: 78%

Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers

Won¹,

Kim²,

Park³

2018

Int. J. Med. Sci.

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Endometriosis, although not malignant, has clinically demonstrated properties of invasiveness and metastasis. The pathogenesis of endometriosis, however, has not yet been elucidated. The immunological differences between endometriosis and malignant gynecologic tumors were analyzed by assessing C-type lectin receptors, which are associated with innate immunity, and immunoglobulin secretion, which is associated with B cell adaptive immunity, in the peritoneal fluid of these patients. Peritoneal fluid samples were obtained from 42 patients with benign masses (control group), 38 with endometriosis, and 43 with gynecologic (ovarian, uterine, and cervical) cancers. The levels of expression in these samples of mRNAs encoding the C-type lectin receptors Dectin-1, MR1, MR2, DC-SIGN, Syk, Card 9, Bcl 10, Malt 1, src, Dec 205, Galectin, Tim 3, Trem 1, and DAP 12, were measured by real-time reverse transcription polymerase chain reaction, and the concentrations of IgG, IgA and IgM were measured by enzyme-linked immunosorbent assays (ELISA). Findings in the three groups were compared. The level of galectin mRNA was significantly lower, and the levels of MR2 and DAP 12 mRNAs significantly higher, in the endometriosis than in the control group (p<0.05 each). Compared with the gynecologic cancer group, the level of Bcl 10 mRNA was significantly lower, and the levels of MR1, MR2, Syk, Card 9, Malt 1, Dec 205, Tim 3, and DAP 12 mRNAs significantly higher, in the endometriosis group (p<0.05 each). The levels of MR2 and DAP 12 mRNAs were significantly higher in the endometriosis than in the control group (p<0.05 each), whereas the level of galectin mRNA was similar in the endometriosis and gynecologic cancer groups. IgA and IgG concentrations in peritoneal fluid were significantly lower in the gynecologic cancer than in the control group (p<0.05 each). However, concentrations of all three immunoglobulins in the endometriosis group did not differ from those in the other two groups (p>0.05). C-type lectin receptors and immunoglobulins act cooperatively and are closely associated in the pathogenesis of endometriosis. The decreased expression of galectin mRNA in the peritoneal fluid of the endometriosis group suggests that endometriosis and gynecologic cancers have similar immunologic characteristics.

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Section: Discussionmentioning

confidence: 78%

Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers

Won¹,

Kim²,

Park³

2018

Int. J. Med. Sci.

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“…Moreover, the levels of expression of mRNAs encoding TLRs-2 and -9 and NODs-1 and -2 were significantly higher in patients with than without endometriosis. Up-regulation of PRR expression and accelerated endometrial proliferation can result in tumor formation 9. Human heat-shock protein 70 has been reported to induce pelvic inflammation, involving the TLR-3 and TLR-4-mediated growth of endometrial cells 5, 10, with TLR-4 having a significant role in innate immune reactions to bacterial endotoxin in patients with endometriosis 4.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Pattern Recognition Receptors and Nitric Oxide Synthase in Patients with Endometriosis

Yeo

Won²,

Lee³

et al. 2013

Int. J. Med. Sci.

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Objective: Endometriosis is characterized by repeated inflammatory changes and serious adhesions, inducing innate and adaptive immune responses within the abdominal cavity. To assess these immune responses, we evaluated the levels of expression of Toll-like receptors (TLR)-1, -2, -4, -5, and -9; nucleotide-binding oligomerization domains (NOD)-1 and -2; interleukins-1β, -6, -8, -10, and -12; interferon-γ; tumor necrosis factor-α; inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS); and immunoglobulins (Igs) in patients with endometriosis.Methods: The levels of TLRs, NODs, cytokines, and NOS mRNAs in peritoneal effusions were assessed by real time reverse transcription-polymerase chain reaction; and IgG, IgA and IgM concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in 40 patients with and 40 without endometriosis. Findings from the two groups were compared.Results: We observed expression of all pattern recognition receptors (PRRs), cytokines, and NOS mRNAs and Igs in the effusion fluid of patients with and without endometriosis. The levels of TLR-2 and -9; NOD-1 and -2; iNOS and eNOS mRNAs and CA 125 were significantly higher in the endometriosis than in the non-endometriosis group (p<0.05 each). Moreover, PRR, cytokine, and NOS expression showed significant correlations (p<0.05).Conclusions: PRRs, cytokines, and NOS, which act cooperatively in the innate immune response, are closely associated with endometriosis. Increased expression of TLR-2, TLR -9, NOD-1, NOD-2, and NOS mRNA in peritoneal fluid may be associated with endometriosis.

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“…For example, the upregulation of PRRs in endometriosis can lead to progression into ovarian endometrioid carcinoma and clear cell carcinoma (47). In particular, carcinogenesis can be accelerated by PRR-induced activation of hepatocyte nuclear factor 1 signaling and dependent oxidative stress (48). TLRs belong to the PRR system and can recognize highly conserved structural motifs of pathogenic microorganisms (49).…”

Section: Microbiome Host Recognition Receptors and Ovarian Cancermentioning

confidence: 99%

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer

et al. 2020

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Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.

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New insights into pattern recognition receptors and their ligands in gynecologic pathologies

Cited by 10 publications

References 81 publications

Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers

Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers

Increased Expression of Pattern Recognition Receptors and Nitric Oxide Synthase in Patients with Endometriosis

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer

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