scholarly journals Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. R199-R207 ◽  
Author(s):  
Leila Pirdel ◽  
Manijeh Pirdel
Keyword(s):  
Iron Overload ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Endometrial Cells ◽  
Retrograde Menstruation ◽  
Wide Range ◽  
Peritoneal Endometriosis ◽  
Macrophage Apoptosis ◽  
Novel Therapeutic Strategies

This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis.

scholarly journals The History of the Discovery of Ectopic Epithelial Cells in Lower Peritoneal Organs: The So-Called Mucosal Invasion

2021 ◽  
Vol 2 (2) ◽  
pp. 68-84
Author(s):  
Marwan Habiba ◽  
Donatella Lippi ◽  
Giuseppe Benagiano
Keyword(s):  
Fallopian Tubes ◽  
Endometrial Cells ◽  
Retrograde Menstruation ◽  
Uterine Mucosa ◽  
Direct Infiltration ◽  
History Of ◽  
Stepwise Evolution ◽  
Ovarian Endometriomas ◽  
Scientific Endeavour

Through microscopy, early researchers identified the epithelium on the inner surfaces of the uterus, cervix and Fallopian tubes. The identification of ectopic epithelium was gradual, starting from the gross pathology study of unusual cystic lesions. Towards the end of the nineteenth century, attention focused on the epithelium as a critical component. The term ‘adenomyoma’ was coined around eighteen eighty to designate the majority of mucosa-containing lesions. Several theories were advanced to explain its aetiology. In the main, lesions were considered to arise from invasion from uterine epithelium; implantation of endometrium through retrograde menstruation; hematogenous or lymphatic spread; or from embryonic remnants. Although initially widely rejected, around 1920, an almost unanimous consensus formed on the endometrial nature of epithelial invasions. During the following years, adenomyosis and endometriosis came to be used to distinguished lesions within or outside the uterus. Adenomyosis was attributed to direct infiltration of uterine mucosa into the myometrium, and endometriosis to the implantation of endometrial cells and stroma into the peritoneal cavity through retrograde menstruation. Around the same time, ovarian lesions, initially described as ovarian hematomas or chocolate cysts, were regarded as a form of endometriosis. Three variants of endometriosis were thus described: superficial peritoneal, deep nodular and ovarian endometriomas. Ectopic epithelium has long been recognised as having similarities to tubal, or cervical epithelium. Lesions containing mixed epithelium are often termed Müllerianosis. This article demonstrates the stepwise evolution of knowledge, the role of the pioneers and the difficulties that needed to be overcome. It also demonstrates the value of collaboration and the inter-connected nature of the scientific endeavour.

scholarly journals Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
T Cell Response ◽  
No Production ◽  
Similar Reduction ◽  
Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

scholarly journals Essential Role of Platelet-Activating Factor in Control of Leishmania (Leishmania)amazonensis Infection

2000 ◽  
Vol 68 (11) ◽  
pp. 6355-6361 ◽  
Author(s):  
Maria Valdrinez Campana Lonardoni ◽  
Momtchillo Russo ◽  
Sonia Jancar
Keyword(s):  
Lymph Nodes ◽  
Platelet Activating Factor ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
Leishmania Infection ◽  
Prostaglandin E ◽  
No Production ◽  
Regional Lymph Nodes

ABSTRACT In the present study we investigated the role of platelet-activating factor (PAF) and prostaglandins in experimental Leishmania (Leishmania)amazonensis infection and the relationship between these mediators and nitric oxide (NO) production. Mouse peritoneal macrophages elicited with thioglicolate were infected with leishmania amastigotes, and the infection index determined 48 h later. The course of infection was monitored for 5 weeks in mice infected in the footpad with promastigotes by measuring the footpad swelling and parasite load in regional lymph nodes and spleen. The addition of PAF to C57BL/6 mouse macrophages significantly inhibited parasite growth and induced NO production. Treatment of macrophages with a selective PAF antagonist, WEB2086, increased the infection, indicating that endogenously produced PAF regulates macrophage ability to control leishmania infection. This effect of PAF was abolished by addition of the inhibitor of NO synthesis, L-NAME, to the cultures. The addition of prostaglandin E2 significantly increased the infection and NO production. Treatment with cyclo-oxygenase inhibitor, indomethacin, reduced the infection and PAF-induced release of NO. Thus, the increased NO production induced by PAF seems to be mediated by prostaglandins. The more-selective inhibitors of cyclo-oxygenase 2, nimesulide and NS-398, had no significant effect. Thus, antileishmanial activity correlates better with the presence of PAF or absence of prostaglandins than with NO production. In vivo treatment with PAF antagonists significantly increased leishmania lesions, as well as the parasite load, in regional lymph nodes and spleens. These findings indicate that PAF is essential for the control of leishmania infection.

scholarly journals Peritoneal endometriosis and infertility

2021 ◽  
Vol 51 (3) ◽  
pp. 70-72
Author(s):  
Е. K. Ailamazyan ◽  
G. A. Savitsky ◽  
D. А. Niauri ◽  
S. M. Gorbushin
Keyword(s):  
Abdominal Cavity ◽  
Ovarian Failure ◽  
Endometrial Receptivity ◽  
Proliferative Potential ◽  
Endometrial Cells ◽  
Retrograde Menstruation ◽  
Peritoneal Endometriosis ◽  
Uterine Infertility

Peritoneal endometriosis and infertility in most of patients (in 80%) are pathogenetically conjugated. Both peritoneal endometriosis and infertility are based in ovarian failure. These women have a low endometrial receptivity for blastocysts implantation (retardation development of glands, vessels, and stroma; changes in the microrelief of the epithelium). Even at the beginning of the menstruation patients with peritoneal endometriosis and infertility have cells with a great adhesive and proliferative potential in the endometrium. This kind of cells have an ability for long autonomous existence. Ovarian failure in these women is a promotion factor for development of the retrograde menstruation. In these conditions the endometrial cells with adhesive potential are frequently bringing in the abdominal cavity. Active endometrium heterotopias support the ovarian failure and create conditions for uterine infertility (implantation disorders).

scholarly journals Iron Overload in Diabetic Retinopathy: A Cause or a Consequence of Impaired Mechanisms?

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Andreea Ciudin ◽  
Cristina Hernández ◽  
Rafael Simó
Keyword(s):  
Diabetic Retinopathy ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Renin Angiotensin System ◽  
Retinal Neurodegeneration ◽  
Novel Therapeutic Strategies

Iron is an essential ion for life, playing a central role in many metabolic processes. The most important property of free iron is its capacity to be reversibly oxidized and reduced, but at same time this make it highly pro-oxidant molecule. In this regard, iron is able to generate powerful reactive oxygen species (ROS). For this reason, careful control on iron availability is central to the maintenance of normal cell function in the retina. In the diabetic eye there is an impairment of iron homeostasis, thus leading to iron overload. The mechanisms involved in this process include: (1) Destruction of heme molecules induced by hyperglycemia (2) Intraretinal and vitreal hemorrhages (3) Overexpression of the renin-angiotensin system. The main consequences of iron overload are the following: (1) Retinal neurodegeneration due to the increase of oxidative stress (2) Increase of AGE-RAGE binding (3) Defective phagocytosis of retinal pigment epithelium, which generates the accumulation of autoantigens and the synthesis of proinflammatory cytokines. Further studies addressed to explore not only the role of iron in the pathogenesis of diabetic retinopathy, but also to design novel therapeutic strategies based on the regulation of iron homeostasis are needed.

Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release

2003 ◽  
Vol 285 (2) ◽  
pp. H722-H726 ◽  
Author(s):  
Seiichi Mochizuki ◽  
Hans Vink ◽  
Osamu Hiramatsu ◽  
Tatsuya Kajita ◽  
Fumiyuki Shigeto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hyaluronic Acid ◽  
Production Rate ◽  
No Production ◽  
Perfusion Rate ◽  
Nitric Oxide Release ◽  
Femoral Arteries ◽  
Wide Range ◽  
Acid Glycosaminoglycans

Endothelium-derived nitric oxide (NO) is synthesized in response to chemical and physical stimuli. Here, we investigated a possible role of the endothelial cell glycocalyx as a biomechanical sensor that triggers endothelial NO production by transmitting flow-related shear forces to the endothelial membrane. Isolated canine femoral arteries were perfused with a Krebs-Henseleit solution at a wide range of perfusion rates with and without pretreatment with hyaluronidase to degrade hyaluronic acid glycosaminoglycans within the glycocalyx layer. NO production rate was evaluated as the product of nitrite concentration in the perfusate and steady-state perfusion rate. The slope that correlates the linear relation between perfusion rate and NO production rate was taken as a measure for flow-induced NO production. Hyaluronidase treatment significantly decreased flow-induced NO production to 19 ± 9% of control (mean ± SD; P < 0.0001 vs. control; n = 11), whereas it did not affect acetylcholine-induced NO production (88 ± 17% of pretreatment level, P = not significant; n = 10). We conclude that hyaluronic acid glycosaminoglycans within the glycocalyx play a pivotal role in detecting and amplifying the shear force of flowing blood that triggers endothelium-derived NO production in isolated canine femoral arteries.

scholarly journals Role of cytokines and nitric oxide in the induction of tuberculostatic macrophage functions

2000 ◽  
Vol 9 (6) ◽  
pp. 261-269 ◽  
Author(s):  
Vera L. Petricevich ◽  
Rosely C. B. Alves
Keyword(s):  
Nitric Oxide ◽  
Culture Media ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Phenotypic Differences ◽  
Ifn Γ ◽  
Necrosis Factor

The aim of this study was to determine phenotypic differences when BCG invades macrophages. Bacilli prepared from the same BCG primary seed, but produced in different culture media, were analysed with respect to the ability to stimulate macrophages and the susceptibility to treatment with cytokines and nitric oxide (NO). Tumour necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, interleukin-6 (IL-6) and interferon γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay (ELISA), whereas NO levels were detected by Griess colorimetric reactions in the culture supernatant of macrophages incubated with IFN-γ , TNF or NO and subsequently exposed to either BCG-I or BCG-S. We found that BCG-I and BCGS bacilli showed different ability to simulate peritoneal macrophages. Similar levels of IL-6 were detected in stimulated macrophages with lysate from two BCG samples. The highest levels of TNF and IFN-γ were observed in macrophages treated with BCG-S and BCG-I, respectively. The highest levels of NO were observed in cultures stimulated for 48h with BCG-S. We also found a different susceptibility of the bacilli to ex ogenous treatm ent w ith IFN-γ and TNF which were capable of killing 60 and 70% of both bacilli, whereas NO was capable of killing about 98 and 47% of BCG-I and BCG-S, respectively. The amount of bacilli proportionally decreased with IFN-γ and TNF, suggesting a cytokine-related cytotox ic effect. Moreover, NO also decreased the viable number of bacilli. Interestingly, NO levels of peritoneal macrophages were significantly increased after cytokine treatment. This indicates that the treatment of macrophages with cytokines markedly reduced bacilli number and presented effects on NO production. The results obtained here emphasize the importance of adequate stimulation for guaranteeing efficient killing of bacilli. In this particular case, the IFN-γ and TNF were involved in the activation of macrophage bactericidal activity.

scholarly journals IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yun Ge ◽  
Juan Chen ◽  
Yanting Hu ◽  
Xinyi Chen ◽  
Man Huang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Peritoneal Macrophages ◽  
Serum Concentrations ◽  
Pyrin Domain ◽  
Downstream Effects ◽  
Macrophage Apoptosis ◽  
Mouse Peritoneal Macrophages

Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury.

scholarly journals Clinical and Serologic Manifestations of Autoimmune Disease in MRL-lpr/lpr Mice Lacking Nitric Oxide Synthase Type 2

1997 ◽  
Vol 186 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Gary S. Gilkeson ◽  
John S. Mudgett ◽  
Michael F. Seldin ◽  
Phil Ruiz ◽  
Audrey A. Alexander ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Immunoblot Analysis ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Renal Vessels ◽  
Dna Antibodies ◽  
Nos Inhibitor ◽  
Oxide Synthase

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL–lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl–arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL–lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL–lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL–lpr/lpr mice to the N4 generation. MRL–lpr/lpr littermates homozygous for disrupted NOS2 (−/−), heterozygous for disrupted NOS2 (+/−), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (−/−) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/−) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (−/−) animals, whereas that of (+/+) was high and (+/−) intermediate. The (−/−) mice developed glomerular and synovial pathology similar to that of the (+/−) and (+/+) mice. However, (−/−) mice and (+/−) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (−/−) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

scholarly journals Cell-to-Cell Interactions Mediating Functional Recovery after Stroke

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3050
Author(s):  
Claudia Alia ◽  
Daniele Cangi ◽  
Verediana Massa ◽  
Marco Salluzzo ◽  
Livia Vignozzi ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Cell Interactions ◽  
Neural Cells ◽  
Cellular Interactions ◽  
Post Stroke ◽  
Wide Range ◽  
Structural Plastic ◽  
Novel Therapeutic Strategies ◽  
Intercellular Connections

Ischemic damage in brain tissue triggers a cascade of molecular and structural plastic changes, thus influencing a wide range of cell-to-cell interactions. Understanding and manipulating this scenario of intercellular connections is the Holy Grail for post-stroke neurorehabilitation. Here, we discuss the main findings in the literature related to post-stroke alterations in cell-to-cell interactions, which may be either detrimental or supportive for functional recovery. We consider both neural and non-neural cells, starting from astrocytes and reactive astrogliosis and moving to the roles of the oligodendrocytes in the support of vulnerable neurons and sprouting inhibition. We discuss the controversial role of microglia in neural inflammation after injury and we conclude with the description of post-stroke alterations in pyramidal and GABAergic cells interactions. For all of these sections, we review not only the spontaneous evolution in cellular interactions after ischemic injury, but also the experimental strategies which have targeted these interactions and that are inspiring novel therapeutic strategies for clinical application.

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