The role of cytokines in both the normal and malignant ovary.

1999 ◽  
pp. 93-107 ◽  
Author(s):  
M A Nash ◽  
G Ferrandina ◽  
M Gordinier ◽  
A Loercher ◽  
R S Freedman
Keyword(s):  
Immune Responses ◽  
Growth Regulation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Rapid Development ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Cytokines And Chemokines ◽  
Normal Ovarian Tissue

Normal ovarian tissue is rich in cytokines. Cytokines and chemokines are important in the physiology of ovarian function and of ovulation. Cytokines and chemokines may recruit cytokine-producing lymphocytes to the site of a developing follicle, and cytokines appear to play an important role in pre and post follicle development. Most of the same cytokines that are found in normal ovarian tissue are also found in association with malignancy in contrast to their functions in normal tissues. It is reasonable to assume that the functions of cytokines associated with malignancy may serve to promote the unregulated growth if tumor cells and metastasis. It is also likely that cytokines produced by tumors will modulate immune responses that favor tumor progression. In the following review, we have highlighted those functions of cytokines that have been identified as having the most significant impact on tumor growth and development. By examining activities of these cytokines in normal and in malignant ovarian tissues, it is hoped that future possible avenues for investigation may be opened up and that the results of these investigations will lead to strategies that can modulate the production or the activity of the cytokines leading to the growth of tumors or their metastases. Such strategies now fall under the general discipline of bioimmunotherapy. This is an expanding discipline as more is learned about growth regulation in cancer, and with the availability and rapid development of new molecules for therapeutic approaches.

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Marius Keller ◽  
Valbona Mirakaj ◽  
Michael Koeppen ◽  
Peter Rosenberger
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
The Future ◽  
Cardiovascular Pathologies ◽  
Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Predictive Value ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Antral Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Positive Parameter ◽  
Primordial Follicles

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

scholarly journals A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity

2007 ◽  
Vol 204 (5) ◽  
pp. 1025-1036 ◽  
Author(s):  
Tae Whan Kim ◽  
Kirk Staschke ◽  
Katarzyna Bulek ◽  
Jianhong Yao ◽  
Kristi Peters ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Toll Like Receptor ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Plasmacytoid Dcs

IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.

scholarly journals Platelet Function in Viral Immunity and SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Afaf Allaoui ◽  
Akif A. Khawaja ◽  
Oussama Badad ◽  
Mariam Naciri ◽  
Marie Lordkipanidzé ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Cytokine Storm ◽  
Blood Components ◽  
Viral Immunity ◽  
Cytokines And Chemokines ◽  
Activated Platelets ◽  
Viral Receptors

AbstractPlatelets, as nonnucleated blood components, are classically recognized for their pivotal role in hemostasis. In recent years, however, accumulating evidence points to a nonhemostatic role for platelets, as active participants in the inflammatory and immune responses to microbial organisms in infectious diseases. This stems from the ability of activated platelets to secrete a plethora of immunomodulatory cytokines and chemokines, as well as directly interplaying with viral receptors. While much attention has been given to the role of the cytokine storm in the severity of the coronavirus disease 2019 (COVID-19), less is known about the contribution of platelets to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we give a brief overview on the platelet contribution to antiviral immunity and response during SARS-CoV-2 infection.

scholarly journals Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas

2006 ◽  
Vol 36 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Christian Fottner ◽  
Timo Minnemann ◽  
Sarah Kalmbach ◽  
Matthias M Weber
Keyword(s):  
Scatchard Analysis ◽  
Mrna Levels ◽  
Therapeutic Approaches ◽  
Binding Studies ◽  
Single Class ◽  
Normal Tissues ◽  
Igf System ◽  
Igf I ◽  
Polymerase Chain

In order to determine the role of the IGF-I receptor (IGF-IR) in human pheochromocytomas we have compared the expression of the IGF-IR in normal tissues and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand binding. By semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the mRNA of the IGF-IR could be detected in all samples of normal adrenomedullary cells (n=13) and pheochromocytomas (n=16). However, pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2.8±0.5×105 molecules/μg RNA vs 7.8±1.2×105 molecules/μg RNA; P < 0.001). This overexpression of the IGF-IR in pheochromocytomas could be confirmed at the protein level by binding studies. Radioligand assays and Scatchard analysis revealed a single class of high affinity IGF-IR binding sites with a similar dissociation constant (Kd: 0.32±0.1 nmol/l vs 0.22±0.08 nmol/l) for both normal adrenomedullary cells and pheochromocytomas. However, specific 125I-labeled IGF-I binding and the calculated receptor concentration were significantly elevated in pheochromocytomas as compared with normal adrenomedullary cells (58.3±5 vs 24.3±12 nmol/kg protein; P < 0.05). In summary, our results demonstrate significant overexpression of the IGF-IR in human pheochromocytomas. This suggests a possible role of the IGF system in the pathogenesis of adrenal neoplasia and thus IGF-IR may be a target for future therapeutic approaches.

Changes in ovarian hormonal status in cervical cancer patients under the influence of combined HPV/chlamydia trachomatis infection.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17019-e17019
Author(s):  
Valeria Bandovkina ◽  
Elena Mikhaylovna Frantsiyants ◽  
Nailya Guskova ◽  
Tatiana Moiseenko ◽  
Marina Vovkochina ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Chlamydia Trachomatis ◽  
Cancer Patients ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Sharp Decrease ◽  
Chlamydia Trachomatis Infection ◽  
Endocrine Status ◽  
Steroid Binding

e17019 Background: The purpose of the study was to analyze hormonal disorders in tissues of histologically unchanged ovaries of patients with cervical cancer infected with HPV/Chlamydia trachomatis. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4), steroid-binding globulin (SBG) and prolactin (PRL) by the ELISA in intact ovaries of 25 patients aged 53.4±3.2 years with cervical cancer T1b-2aN0M0. HPV presence was determined by Е7 protein expression, Chlamydia trachomatis (Ch. tr.) – by IgG and IgА to Ch. tr. and antigen/DNA by ELISA and Real-time PCR. Tissues of intact ovaries obtained during hysterectomy from 22 non-infected women of similar age with endometrial cancer T1N0M0 were used as the control. Results: The data demonstrated a sharp decrease in E2 level by 9.3 times and increase in E1 by 2.3 times in intact ovaries of cervical cancer patients infected with HPV and Ch. tr., compared with the values in controls. Changes were noted in the balance between some estrogen fractions: E1 percentage increased by 5 times, E3 – by 2.4 times and E2 percentage decreased by 4 times. Androgenic status in intact ovaries in cervical cancer was characterized with increased levels of T (by 5.1 times) and fT (by 1.6 times). We noted an increase in SBG concentration by more than 3 times in response to the release of androgens registered in ovarian tissue, as well as significant (by 4.4 times) increase in PRL and decrease in P4 by 1.5 times compared with non-infected tissues. Estrogens to P4 ratio in co-infected patients reduced by 1.6 times, while the PRL to P4 ratio increased by 6.4 times, mainly due to disorders in hormone-producing ovarian function. Conclusions: The development of malignant process in the cervix in a combined HPV and Chlamydia trachomatis infection is accompanied by disorders of the endocrine status in tissues of intact ovaries and shows the undeniable role of consequences of HPV/Chlamydia trachomatis coinfection in this process.

105 P75 Neuronal Cells and Fibers in the Bovine Ovary

2018 ◽  
Vol 30 (1) ◽  
pp. 192
Author(s):  
R. Carrasco ◽  
C. E. Leonardi ◽  
J. Singh ◽  
G. P. Adams
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Surface Epithelium ◽  
Corpora Lutea ◽  
Immunoreactive Neuron ◽  
Engineering Research ◽  
Bovine Ovary

Neurotrophins are molecules involved in the development and survival of neurons and its cellular projections. Results of recent studies have implicated the local role of the high affinity neurotropin receptor, trkA, in bovine ovarian follicle selection and early luteogenesis (Carrasco et al. 2016 Reprod. Biol. Endocrinol. 14, 47), but innervation and neuropeptide control remains an unexplored aspect of ovarian function. P75 is the low-affinity receptor for all neurotrophins and is expressed in ovarian tissue. The objective of this study was to explore the distribution of P75 neurons and fibres within the ovary and to examine the relationship of these components with follicular development. The ovaries of cows (n = 5) were collected at the time of slaughter, 36 h after induced luteolysis (i.e. proestrus). The ovaries were fixed in 4% paraformaldehyde for 48 h, and samples from the ovarian hilus, medulla, and cortex (3 blocks per ovary) were cryo-sectioned (20–50 µm). Tissue sections were incubated for 48 h with a rabbit antibody against rat P75 or a mouse monoclonal antibody against neurofilament. Immunodetection was visualised by an amplification procedure with horseradish peroxidase using nickel DAB as a chromogen. Sections were counterstained with nuclear fast red for follicle identification. Immunoreactive cell bodies were counted in 10 to 20 fields (40×) per section, and data were expressed based on ovarian areas (cortex, medulla, or hilus) as an average count per 40× field per animal. Data among ovarian regions were compared by ANOVA; differences were considered significant when P < 0.05. Antral follicles ≤5 mm displayed strong immunoreactivity in the theca layer, without reaction in the granulosa cells. In contrast, preovulatory follicles were devoid of P75 immuno-reactivity in the theca layer. Oval P75 immunoreactive neuron-like cells were present in all ovarian areas studied. The neuronal nature of the P75 immunoreactive cells was confirmed by the presence of a similar pattern when adjacent sections were stained for neurofilaments, a protein characteristic of neurons. In the stroma of the ovarian cortex and medulla, neurons were present individually (scattered) rather than grouped; however, a dense network of neurons and fibres was detected immediately beneath the ovarian surface epithelium. No differences between the cortex, medulla, and hilus were found in the mean number of immunoreactive cells (10.6 ± 2.8, 14.4 ± 3.6 and 13.9 ± 2.0 cells/40× field, respectively). Immunoreactive neuron-like cells and fibres were in close proximity to blood vessels in the ovarian medulla. Corpora lutea were devoid of P75 immunoreactivity. In conclusion, results document the existence of a neuronal network in the bovine ovary, displaying an association with follicles at different stages of development. The abundance of neuronal components (i.e. neuron cell bodies and axons) in the ovarian stromal and surface epithelium implies a role of innervation (either extrinsic or intrinsic) in the control of ovarian follicular development and function. Research was supported by the Natural Sciences and Engineering Research Council of Canada.

Hyaluronic acid and Regenerative medicine: New insights into the stroke therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Maryam Shahi ◽  
Daruosh Mohammadnejad ◽  
Mohammad Karimipour ◽  
Seyed Hossein Rasta ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Stroke Therapy ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Inflammatory Processes

: Stroke is known as one of very important public health problems which are related to a societal burden and tremendous economic. It has been showed, there are few therapeutic approaches in the treatment of this disease. In this regard, present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neurorecovery. Among these therapies, regenerative medicine-based therapies have been appeared as new ways in stroke therapy. Hyaluronic acid (HA) is a new candidate which could be applied as regerenative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan which is formed of repeating disaccharide units (D-glucuronic acid and N-acetyl-D-glucosamine). Multiple lines evidence demonstrated that HA has critical roles in normal tissues. It can be key players in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of extracellular matrix. HA has very important physicochemical properties (i.e., availability of reactive functional groups and its solubility which makes it as a biocompatible material for applying in the regenerative medicine. Given that HA-based bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic which have introduced them as soft tissue fillers and injectable dermal. Several studies indicated that HA could be employed as new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacology effects via affecting on stroke-related processes. Herein, we have summarized the role of extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies in the treatment of stroke.

scholarly journals Differential and sequential immunomodulatory role of neutrophils and Ly6Chi inflammatory monocytes during antiviral antibody therapy

2020 ◽  
Author(s):  
Jennifer Lambour ◽  
Mar Naranjo-Gomez ◽  
Myriam Boyer-Clavel ◽  
Mireia Pelegrin
Keyword(s):  
Immune Responses ◽  
Antibody Therapy ◽  
Myeloid Cell ◽  
Cell Types ◽  
Retroviral Infection ◽  
Antiviral Immune Response ◽  
Inflammatory Monocytes ◽  
Cytokines And Chemokines

AbstractAntiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-Fcγ Rs interactions. Using a mouse model of retroviral infection, we previously showed a crucial role for immune complexes (ICs) in the enhancement of T-cell responses through FcγR-mediated activation of dendritic cells (DCs). However, IC-FcγR interactions involve different cells of the immune system other than DCs such as neutrophils and monocytes. These two myeloid cell-types are innate effector cells rapidly recruited to sites of infection. In addition to being key cells to fight against invading pathogens, they are also endowed with immunomodulatory properties. While the role of DCs in enhancing antiviral immune responses upon mAb treatment has been addressed in several studies, the role of neutrophils and monocytes has been much less studied. Here we addressed how mAb therapy affects the functional activation of neutrophils and inflammatory monocytes in retrovirus-infected mice. We found that both cell-types activated in vitro by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV expression on neutrophils and inflammatory monocytes and enhanced their cytokines and chemokines secretion. Notably, upon antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the antiviral immune response through the secretion of Th1-type polarizing cytokines and chemokines. Our work provides novel findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon antiviral mAb therapy.

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