267. Interleukin-10 inhibits TNFα synthesis and protects against LPS-induced miscarriage and preterm labour

2005 ◽  
Vol 17 (9) ◽  
pp. 109
Author(s):  
S. A. Robertson ◽  
R. J. Skinner ◽  
A. S. Care
Keyword(s):  
Fetal Growth ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Preterm Labour ◽  
Fetal Loss ◽  
Placental Tissue ◽  
Interleukin 10 ◽  
Null Mutant ◽  
Anti Inflammatory ◽  
In Pregnancy

The immune-deviating and anti-inflammatory cytokine interleukin-10 (IL-10) is expressed throughout pregnancy in the decidual and placental tissues. Mice with a null mutation in the IL-10 gene mice are fertile with no reduction in litter size, although fetal growth trajectories and placental structure are altered. IL-10 is known to terminate inflammatory responses and to limit inflammation-induced tissue pathology by inhibiting macrophage synthesis of tumor necrosis factor-α (TNFα). To investigate the anti-inflammatory role of IL-10 in pregnancy, the susceptibility of null mutant mice to low dose LPS-induced miscarriage and preterm labour has been evaluated. When IL-10 null mutant C57Bl/6 (IL-10–/–) and control (IL-10+/+) mice were given low dose E.coli LPS on d10 of pregnancy, IL-10 deficiency was associated with greater fetal loss with fewer mated IL-10–/– mice carrying viable fetuses at day 18 and increased rate of fetal resorption. In mice treated with LPS on day 17, preterm delivery within 24 h occurred in a higher proportion of IL-10–/– mice than IL-10+/+ mice. LPS induced very high and sustained TNFα and IL-6 content in serum, uterine and placental tissue in IL-10–/– mice, associated with upregulated mRNA expression of both cytokines in gestational tissues. These data show that IL-10 modulates placental resistance to inflammatory stimuli by down-regulating expression of the pro-inflammatory cytokines TNFα and IL-6. We conclude that IL-10 has a dual role in pregnancy, acting to regulate placental morphogenesis and fetal growth trajectory, and to protect against inflammation-induced miscarriage and preterm labour.

scholarly journals Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone as an Anti-Inflammatory Modulator of LPS-Mediated Astrocyte Responses

2020 ◽  
Vol 21 (21) ◽  
pp. 8203 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Arina I. Nikolskaya ◽  
Sergei V. Goriainov ◽  
Alina A. Astakhova ◽  
Marina G. Sergeeva
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Acid Synthesis ◽  
Interleukin 10 ◽  
Ultra Performance Liquid Chromatography ◽  
Necrosis Factor Alpha ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory ◽  
Ha Synthase

Astrocytes are glial cells that play an important role in neuroinflammation. Astrocytes respond to many pro-inflammatory stimuli, including lipopolysaccharide (LPS), an agonist of Toll-like receptor 4 (TLR4). Regulatory specificities of inflammatory signaling pathways are still largely unknown due to the ectodermal origin of astrocytes. Recently, we have shown that hyaluronic acid (HA) may form part of astrocyte inflammatory responses. Therefore, we tested 4-methylumbelliferone (4-MU), a specific inhibitor of HA synthesis, as a possible regulator of LPS-mediated responses. Rat primary astrocytes were treated with LPS with and without 4-MU and gene expression levels of inflammatory (interleukins 1β, (IL-1β), 6, (IL-6), tumor necrosis factor alpha TNFα,) and resolution interleukin 10 (IL-10) markers were evaluated via real-time PCR and western blot. The release of cytokines and HA was determined by ELISA. Oxylipin profiles were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Our data show that 4-MU (i) has anti-inflammatory effects in the course of TLR4 activation, decreasing the cytokines level TNFα, IL-6 and IL-1β and increasing IL-10, (ii) downregulates prostaglandin synthesis but not via cyclooxygenases COX-1 and COX-2 pathways, (iii) modulates HA synthesis and decreases LPS-induced HA synthase mRNA expression (HAS-1, HAS-2) but does not have an influence on HAS-3, HYAL1 and HYAL2 mRNAs; (iv) the effects of 4-MU are predominantly revealed via JNK but not p38, ERK mitogen-activated protein kinases (MAPKs) or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathways. For the first time, it is shown that 4-MU possesses the useful potential to regulate an inflammatory astrocyte response.

scholarly journals Monocolonization of Germ-Free Mice withBacteroides fragilisProtects against Dextran Sulfate Sodium-Induced Acute Colitis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chien-Chao Chiu ◽  
Yung-Hao Ching ◽  
Yu-Chih Wang ◽  
Ju-Yun Liu ◽  
Yen-Peng Li ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Interleukin 10 ◽  
Myeloperoxidase Activity ◽  
Acute Colitis ◽  
Germ Free ◽  
Intestinal Immune System ◽  
Anti Inflammatory

Ulcerative colitis is inflammatory conditions of the colon caused by interplay of genetic and environmental factors. Previous studies indicated that the gut microflora may be involved in the colonic inflammation.Bacteroides fragilis(BF) is a Gram-negative anaerobe belonging to the colonic symbiotic. We aimed to investigate the protective role ofBFin a colitis model induced in germ-free (GF) mice by dextran sulfate sodium (DSS). GF C57BL/6JNarl mice were colonized withBFfor 28 days before acute colitis was induced by DSS.BFcolonization significantly increased animal survival by 40%, with less reduction in colon length, and decreased infiltration of inflammatory cells (macrophages and neutrophils) in colon mucosa following challenge with DSS. In addition,BFcould enhance the mRNA expression of anti-inflammatory-related cytokine such as interleukin 10 (IL-10) with polymorphism cytokineIL-17and diminish that of proinflammatory-related tumor necrosis factorαwith inducible nitric oxide synthase in the ulcerated colon. Myeloperoxidase activity was also decreased inBF-DSS mice. Taking these together, theBFcolonization significantly ameliorated DSS-induced colitis by suppressing the activity of inflammatory-related molecules and inducing the production of anti-inflammatory cytokines.BFmay play an important role in maintaining intestinal immune system homeostasis and regulate inflammatory responses.

Low-dose theophylline does not exert its anti-inflammatory effects in mild asthma through upregulation of interleukin-10 in alveolar macrophages

Allergy ◽  
2001 ◽  
Vol 56 (11) ◽  
pp. 1087-1090 ◽  
Author(s):  
B. Oliver ◽  
K. Tomita ◽  
A. Keller ◽  
G. Caramori ◽  
I. Adcock ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Low Dose ◽  
Interleukin 10 ◽  
Mild Asthma ◽  
Anti Inflammatory

scholarly journals Role of low dose ecosprin and heparin in achieving live births in pregnancy with thrombophilia

2017 ◽  
Vol 6 (12) ◽  
pp. 5261
Author(s):  
Shilpa Asthana ◽  
Bandana Sodhi ◽  
Satish Kumar
Keyword(s):  
Low Dose ◽  
Previous History ◽  
Fetal Loss ◽  
Obstetric Outcomes ◽  
Obstetric Outcome ◽  
Live Births ◽  
History Of ◽  
Chi Square Analysis ◽  
In Pregnancy

Background: Thrombophilia is a disorder of haemostatic system that results in increased tendency of thrombus formation in both venous and arterial vascular system. The thrombotic events are not only restricted to venous thromboembolism but also can cause fetal loss (abortions or recurrent abortions and fetal demise), placental abruption, intrauterine growth restriction and severe pre-eclampsia. This study evaluates the role of administering thromboprophylaxis with heparin and ecosprin to patients with thrombophilia in pregnancy with previous history of adverse obstetric outcomes.Methods: This prospective study was conducted in 60 patients diagnosed with thrombophilia during pregnancy. The objective of the study was to determine the role of administering low dose ecosprin and heparin as thromboprophylaxis in achieving live births in these patients with thrombophilia. All patients included in this study were prophylactically administered low dose ecosprin with either unfractionated heparin (5000 IU s.c, BD) or low molecular weight heparin (40 mg s.c, OD) during pregnancy. Patients were followed up in the antenatal period and the obstetric outcome noted. Comparisons were made between the obstetric outcomes of these patients receiving the aforesaid thromboprophylaxis with those of previous untreated pregnancies during which no ecosprin or heparin had been administered. The data obtained were subjected to statistical analysis using Students ‘t’ test and Chi square analysis. P value <0.05 was considered statistically significant.Results: Fifty nine of the sixty patients with thrombophilia and previous adverse pregnancy outcome who received prophylaxis with ecosprin and heparin during the present pregnancy had live births (98.33%; p <0.0001). Fifty-eight (96.66%) of these patients progressed to term delivery and one (1.67%) pregnancy resulted in a pre-term birth.Conclusions: Present study reveals that prophylaxis with low dose ecosprin and heparin administered to patients with thrombophilia (acquired or inherited) with history of previous adverse obstetric outcome resulted in a positive outcome in terms of a significantly higher number of live births. However, larger studies are needed to further elaborate on the role of thromboprophylaxis in pregnancies with inherited thrombophilia.

scholarly journals Alpha 1-antitrypsin ameliorates ventilator-induced lung injury in rats by inhibiting inflammatory responses and apoptosis

2017 ◽  
Vol 243 (1) ◽  
pp. 87-95 ◽  
Author(s):  
He Zhu ◽  
Jianshuai He ◽  
Jia Liu ◽  
Xin Zhang ◽  
Fengyun Yang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Treatment Options ◽  
Weight Ratio ◽  
Interleukin 10 ◽  
Male Rats ◽  
Ventilator Induced Lung Injury ◽  
Anti Inflammatory ◽  
Alpha 1 Antitrypsin

Mechanical ventilation is extensively used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). The present study investigated the protective effect of alpha 1-antitrypsin (AAT) on VILI. Adult male rats were subjected to sham, ventilation + saline, or ventilation + AAT treatment and lung injuries were evaluated. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained to assess systemic and local inflammatory responses, respectively. Mechanical ventilation resulted in lung injury, as evidenced by histological abnormalities as well as elevations in PaO2/FiO2 ratio, the wet-to-dry weight ratio, and the BALF level of proteins. The intravenous administration of AAT significantly improved these parameters of lung function, suggesting a protective role of AAT in VILI. Mechanistically, ventilator-induced inflammation was effectively reduced by AAT, as evidenced by decreases in BALF neutrophil counts, BALF cytokines, and serum adhesion factors. In contrast, anti-inflammatory interleukin-10 in BALF was increased in response to AAT. AAT treatment also inhibited the expression of nuclear factor-κB, Bax, and cleaved caspase-3 while promoting Bcl-2 expression in ventilator-injured lung tissues. AAT treatment can ameliorate VILI by inhibiting inflammatory mediator production and apoptosis. Impact statement Mechanical ventilation has been commonly used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). Few effective treatment options are currently available to reduce VILI. Alpha 1-antitrypsin (AAT) is an inhibitor of serine protease with anti-inflammatory and antiapoptotic properties, suggesting a possible role in attenuating lung injury. The present study demonstrates that AAT inhibits the development of VILI by modulating inflammation- and apoptosis-related protein expression. Therefore, AAT may be a novel therapeutic agent for acute respiratory distress syndrome patients undergoing mechanical ventilation.

scholarly journals The Strand Specific Regulation of miR-155-3p in Response to Lipopolysaccharide and Interleukin-10 Stimulation Requires FUBP1 Protein

2021 ◽  
Author(s):  
Jeff S. J. Yoon ◽  
Abdulwadood Baksh ◽  
Thomas C. Chamberlain ◽  
Alice L-F. Mui
Keyword(s):  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Activated Macrophages ◽  
Anti Inflammatory ◽  
Specific Regulation ◽  
Anti Inflammatory Cytokine

MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.

scholarly journals Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

2016 ◽  
Vol 84 (6) ◽  
pp. 1761-1774 ◽  
Author(s):  
Luciana V. de Moraes ◽  
Sebastien Dechavanne ◽  
Patrícia M. Sousa ◽  
André Barateiro ◽  
Sónia F. Cunha ◽  
...  
Keyword(s):  
Maternal Mortality ◽  
Placental Malaria ◽  
Fetal Loss ◽  
Placental Tissue ◽  
Fetal Weight ◽  
Content Type ◽  
Extracellular Region ◽  
Exported Protein ◽  
In Pregnancy

Plasmodium falciparuminfection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on theP. falciparumIE membrane.Plasmodium bergheiIE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenicP. bergheiparasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) fused to aP. bergheiexported protein (EMAP1) and characterize a var2CSA-based mouse model of PM. BALB/c mice were infected at midgestation with different doses ofP. berghei-var2CSA (P. berghei-VAR) orP. bergheiwild-type IEs. Infection with 104P. berghei-VAR IEs induced a higher incidence of stillbirth and lower fetal weight thanP. berghei. At doses of 105and 106IEs,P. berghei-VAR-infected mice showed increased maternal mortality during pregnancy and fetal loss, respectively. Parasite loads in infected placentas were similar between parasite lines despite differences in maternal outcomes. Fetal weight loss normalized for parasitemia was higher inP. berghei-VAR-infected mice than inP. berghei-infected mice.In vitroassays showed that higher numbers ofP. berghei-VAR IEs thanP. bergheiIEs adhered to placental tissue. Immunization of mice withP. berghei-VAR elicited IgG antibodies reactive to DBL1-6 recombinant protein, indicating that the topology of immunogenic epitopes is maintained between DBL1-6–EMAP1 onP. berghei-VAR and recombinant DBL1-6 (recDBL1-6). Our data suggested that impairments in pregnancy caused byP. berghei-VAR infection were attributable to var2CSA expression. This model provides a tool for preclinical evaluation of protection against PM induced by approaches that target var2CSA.

scholarly journals Interleukin 10 and Tumor Necrosis Factor-Alpha in Pregnancy: Aspects of Interest in Clinical Obstetrics

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Jusciele Brogin Moreli ◽  
Ana Maria Cirino Ruocco ◽  
Joice Monaliza Vernini ◽  
Marilza Vieira Cunha Rudge ◽  
Iracema Mattos Paranhos Calderon
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Fetal Loss ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Study Results ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
In Pregnancy

The purpose of this study was to review the literature regarding the action of the cytokines interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnancy and to emphasize the factors that are of interest to clinical obstetrics. The literature highlights several actions of IL-10 and TNF-α during pregnancy. The actions of these cytokines seem to be antagonistic and dependent on the balance between them, which is orchestrated by the specific immunosuppressive action of IL-10. TNF-α has a characteristic inflammatory action, and it is an additional diabetogenic factor in pregnancy. The loss of the control of the production of these cytokines, with increase of TNF-α, is related to the risk for developing obstetric complications, particularly recurrent fetal loss, gestational diabetes mellitus, hypertensive syndromes, and fetal growth restriction. However, study results are controversial and are not clearly defined. These issues are attributed to the heterogeneity of the studies, particularly regarding their sample sizes and sources, the evaluation methods, and the multiplicity of factors and conditions that influence cytokine production. These questions are fundamental and should be addressed in future investigations to obtain more consistent results that can be applied to obstetric practice.

scholarly journals Necrotizing Fasciitis: Low-Dose Radiotherapy as a Potential Adjunct Treatment

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581987175 ◽  
Author(s):  
Gaurav Dhawan ◽  
Rachna Kapoor ◽  
Asha Dhamija ◽  
Ravinder Singh ◽  
Bharat Monga ◽  
...  
Keyword(s):  
Necrotizing Fasciitis ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Adjunct Treatment ◽  
Inflammatory Conditions ◽  
Low Dose Radiotherapy ◽  
Cost Of Health Care ◽  
Anti Inflammatory ◽  
Effective Use

Necrotizing fasciitis (NF) is a rapidly spreading bacterial infection causing extensive tissue necrosis and destruction. Despite appropriate therapy, the disease results in significant morbidity/mortality and substantial treatment costs. Several studies published in the early 1900s demonstrated the effective use of low-dose X-ray radiotherapy (RT) for the treatment of many diverse inflammatory conditions and diseases (eg, gas gangrene, sinus infections, arthritis, tendonitis, and serious inflammatory lung conditions). The mechanism by which therapeutic RT doses produce positive patient outcomes is related at least in part to its capacity to induce tissue-based anti-inflammatory responses. This action is due to the polarization of macrophages to an anti-inflammatory or M2 phenotype via optimized low-dose RT. Low-dose RT has the potential to significantly reduce debilitating surgeries and aggressive treatments required for NF, providing a 3-prong benefit in terms of patient mortality, length of hospitalization stays, and cost of health care (both short term and long term). Low cost and easy availability of low-dose RT makes it a potentially useful option for patients of every age-group. In addition, low-dose RT may be a particularly useful option in countries treating many patients who are unable to afford surgeries, antibiotics, and hyperbaric oxygen.

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