Aminophylline and progesterone prevent inflammation-induced preterm parturition in the mouse†

2019 ◽  
Vol 101 (4) ◽  
pp. 813-822 ◽  
Author(s):  
Bronwen R Herbert ◽  
Danijela Markovic ◽  
Ektoras Georgiou ◽  
Pei F Lai ◽  
Natasha Singh ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Phosphodiesterase Inhibitor ◽  
Adenosine Monophosphate ◽  
Cytokine Gene Expression ◽  
Intracellular Camp ◽  
Myometrial Cells ◽  
Anti Inflammatory ◽  
Camp Levels

Abstract Although progesterone (P4) supplementation is the most widely used therapy for the prevention of preterm labor (PTL), reports of its clinical efficacy have been conflicting. We have previously shown that the anti-inflammatory effects of P4 can be enhanced by increasing intracellular cyclic adenosine monophosphate (cAMP) levels in primary human myometrial cells. Here, we have examined whether adding aminophylline (Am), a non-specific phosphodiesterase inhibitor that increases intracellular cAMP levels, to P4 might improve its efficacy using in vivo and in vitro models of PTL. In a mouse model of lipopolysaccharide (LPS)-induced PTL, we found that the combination of P4 and Am delayed the onset of LPS-induced PTL, while the same dose of P4 and Am alone had no effect. Pup survival was not improved by either agent alone or in combination. Myometrial prolabor and inflammatory cytokine gene expression was reduced, but the reduction was similar in P4 and P4/Am treated mice. There was no effect of the combination of P4 and Am on an ex vivo assessment of myometrial contractility. In human myometrial cells and myometrial tissue explants, we found that the combination had marked anti-inflammatory effects, reducing cytokine and COX-2 mRNA and protein levels to a greater extent than either agent alone. These data suggest that the combination of P4 and Am has a more potent anti-inflammatory effect than either agent alone and may be an effective combination in women at high-risk of PTL.

scholarly journals Anti-Allergic and Anti-Inflammatory Effects of Undecane on Mast Cells and Keratinocytes

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1554
Author(s):  
Dabin Choi ◽  
Wesuk Kang ◽  
Taesun Park
Keyword(s):  
Mast Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Allergic Diseases ◽  
Intracellular Camp ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Skin Conditions ◽  
Factor Α ◽  
Camp Levels

The critical roles of keratinocytes and resident mast cells in skin allergy and inflammation have been highlighted in many studies. Cyclic adenosine monophosphate (cAMP), the intracellular second messenger, has also recently emerged as a target molecule in the immune reaction underlying inflammatory skin conditions. Here, we investigated whether undecane, a naturally occurring plant compound, has anti-allergic and anti-inflammatory activities on sensitized rat basophilic leukemia (RBL-2H3) mast cells and HaCaT keratinocytes and we further explored the potential involvement of the cAMP as a molecular target for undecane. We confirmed that undecane increased intracellular cAMP levels in mast cells and keratinocytes. In sensitized mast cells, undecane inhibited degranulation and the secretion of histamine and tumor necrosis factor α (TNF-α). In addition, in sensitized keratinocytes, undecane reversed the increased levels of p38 phosphorylation, nuclear factor kappaB (NF-κB) transcriptional activity and target cytokine/chemokine genes, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and interleukin-8 (IL-8). These results suggest that undecane may be useful for the prevention or treatment of skin inflammatory disorders, such as atopic dermatitis, and other allergic diseases.

Chloroquine stimulates absorption and inhibits secretion of ileal water and electrolytes

1982 ◽  
Vol 243 (2) ◽  
pp. G117-G126
Author(s):  
R. Fogel ◽  
G. W. Sharp ◽  
M. Donowitz
Keyword(s):  
Cholera Toxin ◽  
Calcium Content ◽  
Intracellular Camp ◽  
Rabbit Ileum ◽  
Camp Content ◽  
Serosal Surface ◽  
Ileal Absorption ◽  
Camp Levels

The effects of chloroquine diphosphate, a drug with "'membrane-stabilizing" properties, were studied on basal ileal absorption and on ileal secretion induced by increased intracellular cAMP levels and calcium (serotonin). The studies were performed on rat (in vivo) and rabbit ileum (in vitro). Intraluminal chloroquine (10(-4) M) reversed cholera toxin- and theophylline-induced secretion in rat ileum but did not alter the cholera toxin- and theophylline-induced increases in cAMP content. Addition of chloroquine (10(-4) M) to the mucosal surface of rabbit ileum did not alter basal active electrolyte transport or the serotonin-induced decreased Na and Cl absorption but inhibited the theophylline-induced C1 secretion. Addition of chloroquine (10(-4)) M) to the serosal surface stimulated net Na and Cl absorption. This effect may involve intracellular calcium. Chloroquine increased the rabbit ileal calcium content and decreased 45Ca2+ influx from the serosal surface. Both the mucosal and serosal effects of chloroquine described led to a net increase in absorptive function of the intestine and should prove useful in developing treatment of diarrheal diseases.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

239 USE OF CYCLIC ADENOSINE MONOPHOSPHATE MODULATORS IN IN VITRO PRODUCTION OF BOVINE EMBRYOS

2015 ◽  
Vol 27 (1) ◽  
pp. 209
Author(s):  
T. Fanti ◽  
N. M. Ortega ◽  
R. Garaguso ◽  
M. J. Franco ◽  
C. Herrera ◽  
...  
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Basal Medium ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Hatching Rate ◽  
Bovine Embryos ◽  
Oocyte Competence

In vitro embryo production systems (IVP) try to emulate and enhance molecular events that occur in in vivo reproductive systems in order to increase, not only the number of embryos generated, but also their quality. Despite advances, IVP processes are still inefficient compared with in vivo systems. Several studies have attributed this deficiency to a lack of oocyte competence due to spontaneous premature resumption of meiotic maturation in the oocyte following the removal from its follicular environment. Therefore, our objective was to increase oocyte competence avoiding premature resumption of meiosis by using cyclic adenosine monophosphate modulators. Cumulus-oocyte complexes (COC) were obtained from ovaries of slaughterhouses, washed, and randomly allocated in 2 culture systems. Oocytes in the control group (IVM) were cultured for a period of 24 h in basal medium TCM-199 with EGF (1 µg mL–1) supplemented with rhFSH (25 mIU mL–1). Oocytes in the biphasic in vitro maturation (b-IVM) group were cultured for 2 h in a basal medium supplemented with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 500 µM), and an activator of adenylate cyclase (forskolin, 100 µM). Subsequently, COC were washed and cultured in basal medium supplemented with cilostamide (20 µM) and rhFSH (25 mIU mL–1) for 24 h. Maturation rates were analysed and IVF was performed with a dose of 1 × 106 sperm cells mL–1 in IVF-SOF medium. The presumptive zygotes were cultured in continuous-single-culture medium (Irvine) supplemented with 8 mg mL–1 of BSA until they reached the blastocyst stage. No significant differences in maturation, cleavage, and cryotolerance were observed between b-IVM and IVM groups (P > 0.05; Table 1). This study showed that b-IVM produced a significant increase in IVP compared with the control (IVM) at Days 7 and 8 (P < 0.01). Blastocyst hatching rate was significant (P < 0.05) for both treatment and day of analysis. The b-IVM group yielded an increase of 10 and 7.5% at Days 7 and 8, respectively, of IVP. The biphasic maturation showed an improvement in quality regarding the control group, in the timing analysis of production, and hatching percentages, and these results show that the use of cyclic adenosine monophosphate modulators in the oocyte maturation process enhances oocyte competence, which is reflected in increased productivity and embryo quality. We propose this treatment as an alternative to the standard protocols currently used in IVP of bovine embryos. Table 1.Effect of treatment on maturation, cleavage, and cryotolerance

scholarly journals microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

2020 ◽  
Vol 11 ◽  
Author(s):  
Stephen Fitzsimons ◽  
Silvia Oggero ◽  
Robyn Bruen ◽  
Cathal McCarthy ◽  
Moritz J. Strowitzki ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Ex Vivo ◽  
Macrophage Polarization ◽  
Chronic Inflammatory Disease ◽  
Cholesterol Diet ◽  
Human Coronary Artery ◽  
Inflammatory Signaling ◽  
Anti Inflammatory

BackgroundAtherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).MethodsmiR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.ResultsHere, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.ConclusionmiR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

scholarly journals Sorbaria kirilowii Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 741 ◽  
Author(s):  
Jiwon Jang ◽  
Jong Sub Lee ◽  
Young-Jin Jang ◽  
Eui Su Choung ◽  
Wan Yi Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Inflammatory Activity ◽  
No Production ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.

258 IMPACT OF MILRINONE AND FORSKOLIN ON THE EFFICIENCY AND QUALITY OF BOVINE OOCYTE IN VITRO MATURATION

2013 ◽  
Vol 25 (1) ◽  
pp. 277
Author(s):  
E. Stachowiak ◽  
K. Papis ◽  
J. Karasiewicz ◽  
J. A. Modlinski
Keyword(s):  
In Vitro Maturation ◽  
Combined Treatment ◽  
Phosphodiesterase Inhibitor ◽  
Microscopic Analysis ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Experimental Conditions ◽  
Oocyte Meiosis

The efficiency of in vitro maturation (IVM) of bovine oocytes remains inferior compared with maturation in vivo. Recently, some modifications of in vitro maturation (IVM) procedures have been proposed, such as simulated physiological maturation (Gilchrist 2011 Reprod. Fertil. Dev. 23, 23–31). In our experiment, a comparison of the traditional IVM efficiency with maturation after oocyte meiosis inhibition using roscovitine or with a modified two-step maturation using forskolin (cyclic adenosine monophosphate stimulator) and milrinone (type-3 phosphodiesterase inhibitor) was performed. Control oocytes obtained from slaughterhouse-derived ovaries were subjected to the traditional 24-h maturation in TCM-199 medium supplemented with sodium pyruvate, l-glutamine, gentamicin, 10% FCS, and hormones (pregnant mare’s serum gonadotropin and hCG, PG 600, Intervet, Kenilworth, NJ, USA). The roscovitine (50 µM, 24 h) inhibitory treatment was accomplished in the same medium (without hormones) and subsequently, traditional 24-h IVM was performed. The same TCM-199 medium (with hormones) supplemented with forskolin (100 µM) and milrinone (50 µM) was used for the first step (17 h) of the two-step maturation, whereas the second step (7 h) was performed in the same TCM-199 medium devoid of forskolin and milrinone. Fertilization with frozen sperm processed using TALP media was performed in TALP supplemented with heparin, penicillamine, hypotaurine, epinephrine, and BSA. In vitro culture of presumptive zygotes was performed in CR1aa medium. Portions of oocytes from all treatments after maturation and after fertilization procedures were stained and subjected to microscopic analysis. There were no differences in terms of maturation and fertilization rates between treatments. However, roscovitine-mediated inhibition of maturation performed in our experimental conditions was efficient and reversible, but harmful for subsequent embryo development. On the other hand, two-step maturation was equally as efficient as (but not better than) traditional IVM in all aspects examined in the present study (Table 1). In conclusion, the forskolin and milrinone combined treatment during the IVM procedure gives hope for fully efficient IVM. However, to achieve this goal, more research is necessary. Table 1.Development of embryos after different oocyte maturation procedures1

LIPID NANOPARTICLES FOR TRANSDERMAL DELIVERY OF CELECOXIB: AN IN VITRO AND IN VIVO INVESTIGATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (08) ◽  
pp. 38-48
Author(s):  
S. V Shinde ◽  
S Nikam ◽  
P Raut ◽  
M. K. Ghag ◽  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Ex Vivo ◽  
Research Work ◽  
Lipid Nanoparticles ◽  
Inflammatory Activity ◽  
Promising Alternative ◽  
Solid Lipid ◽  
Anti Inflammatory

In the present research work, celecoxib (CXB) loaded solid lipid nanoparticles (SLNs) were prepared using the probe sonication method, wherein Glyceryl monostearate and Tween 80 were used as solid lipid and surfactant, respectively. To obtain the statistically optimized batch, 32 factorial design was applied. The optimized batch was characterized physicochemically and evaluated through DSC, SEM and XRD studies. The mean particle size of the optimized batch was found to be 135.41± 0.24 nm with a mean % entrapment efficiency of 80 ± 1.69%. The optimized batch was further lyophilized and dispersed into 1% w/v Carbopol 934P to form a gel. Prepared gel was further evaluated for in vitro drug release, occlusivity, ex vivo permeability, local toxicity, in vivo anti-inflammatory activity and accelerated stability study. The study resulted in stable, safe and prolonged anti-inflammatory activity with quick onset of action. Hence, celecoxib loaded solid lipid nanoparticles can be considered as promising alternative to conventional topical systems.

scholarly journals Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 378 ◽  
Author(s):  
Azahara Rodríguez-Luna ◽  
Javier Ávila-Román ◽  
María González-Rodríguez ◽  
María Cózar ◽  
Antonio Rabasco ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antioxidant Properties ◽  
Epidermal Hyperplasia ◽  
Topical Formulation ◽  
Tnf Α ◽  
Skin Erythema ◽  
Cox 2 ◽  
Anti Inflammatory

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.

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