Bacopamonnieri (L.) exerts anti-inflammatory effects on cells of the innate immune system in vitro

2014 ◽  
Vol 5 (3) ◽  
pp. 517-520 ◽  
Author(s):  
Roderick Williams ◽  
Gerald Münch ◽  
Erika Gyengesi ◽  
Louise Bennett
Keyword(s):  
Immune System ◽  
Acute Pain ◽  
Innate Immune System ◽  
Selective Inhibition ◽  
Innate Immune ◽  
Inflammatory Activity ◽  
Consequent Reduction ◽  
Cox 2 ◽  
Anti Inflammatory

Bacopa monnieri(L., BM) is a traditional Ayurvedic medicinal herb recognised for its efficacy in relieving acute pain and inflammation, as related to selective inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2-mediated prostanoid mediators. Anti-inflammatory activity of BM might also account for its benefits in cognition.

scholarly journals Interaction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype Newport

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
George Sakoulas ◽  
Monika Kumaraswamy ◽  
Armin Kousha ◽  
Victor Nizet
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Innate Immune System ◽  
Salmonella Enterica ◽  
Clinical Performance ◽  
Innate Immune ◽  
Content Type ◽  
Antimicrobial Assay

ABSTRACT It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo. This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing cathelicidin LL-37, whole-blood, and neutrophil killing assays. Ceftriaxone and ciprofloxacin were found to be synergistic in vitro against Salmonella enterica serotype Newport. Ceftriaxone, ciprofloxacin, and azithromycin each demonstrated synergy with the human cathelicidin defense peptide LL-37 in killing Salmonella. Exposure of Salmonella to sub-MICs of ceftriaxone resulted in enhanced susceptibility to LL-37, whole blood, and neutrophil killing. The activity of antibiotics in vivo against Salmonella may be underestimated in bacteriologic media lacking components of innate immunity. The pharmacodynamic interactions of antibiotics used to treat Salmonella with each other and with components of innate immunity warrant further study in light of recent findings showing in vivo selection of antimicrobial resistance by single agents in this pathogen. IMPORTANCE It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo.

scholarly journals Mycobacterium avium Biofilm Attenuates Mononuclear Phagocyte Function by Triggering Hyperstimulation and Apoptosis during Early Infection

2013 ◽  
Vol 82 (1) ◽  
pp. 405-412 ◽  
Author(s):  
Sasha J. Rose ◽  
Luiz E. Bermudez
Keyword(s):  
Immune System ◽  
Mycobacterium Avium ◽  
Innate Immune System ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Bacterial Killing ◽  
Content Type ◽  
Tnf Α

ABSTRACTMycobacterium aviumsubsp.hominissuisis an opportunistic human pathogen that has been shown to form biofilmin vitroandin vivo. Biofilm formationin vivoappears to be associated with infections in the respiratory tract of the host. The reasoning behind howM. aviumsubsp.hominissuisbiofilm is allowed to establish and persist without being cleared by the innate immune system is currently unknown. To identify the mechanism responsible for this, we developed anin vitromodel using THP-1 human mononuclear phagocytes cocultured with establishedM. aviumsubsp.hominissuisbiofilm and surveyed various aspects of the interaction, including phagocyte stimulation and response, bacterial killing, and apoptosis.M. aviumsubsp.hominissuisbiofilm triggered robust tumor necrosis factor alpha (TNF-α) release from THP-1 cells as well as superoxide and nitric oxide production. Surprisingly, the hyperstimulated phagocytes did not effectively eliminate the cells of the biofilm, even when prestimulated with gamma interferon (IFN-γ) or TNF-α or cocultured with natural killer cells (which have been shown to induce anti-M. aviumsubsp.hominissuisactivity when added to THP-1 cells infected with planktonicM. aviumsubsp.hominissuis). Time-lapse microscopy and the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay determined that contact with theM. aviumsubsp.hominissuisbiofilm led to early, widespread onset of apoptosis, which is not seen until much later in planktonicM. aviumsubsp.hominissuisinfection. Blocking TNF-α or TNF-R1 during interaction with the biofilm significantly reduced THP-1 apoptosis but did not lead to elimination ofM. aviumsubsp.hominissuis. Our data collectively indicate thatM. aviumsubsp.hominissuisbiofilm induces TNF-α-driven hyperstimulation and apoptosis of surveilling phagocytes, which prevents clearance of the biofilm by cells of the innate immune system and allows the biofilm-associated infection to persist.

scholarly journals Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis

2013 ◽  
Vol 81 (7) ◽  
pp. 2334-2346 ◽  
Author(s):  
Eric D. Holbrook ◽  
Katherine A. Smolnycki ◽  
Brian H. Youseff ◽  
Chad A. Rappleye
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Histoplasma Capsulatum ◽  
Reactive Oxygen ◽  
Innate Immune ◽  
Respiratory Pathogen ◽  
Human Neutrophils ◽  
Content Type

ABSTRACTHistoplasma capsulatumis a respiratory pathogen that infects phagocytic cells. The mechanisms allowingHistoplasmato overcome toxic reactive oxygen molecules produced by the innate immune system are an integral part ofHistoplasma's ability to survive during infection. To probe the contribution ofHistoplasmacatalases in oxidative stress defense, we created and analyzed the virulence defects of mutants lacking CatB and CatP, which are responsible for extracellular and intracellular catalase activities, respectively. Both CatB and CatP protectedHistoplasmafrom peroxide challengein vitroand from antimicrobial reactive oxygen produced by human neutrophils and activated macrophages. Optimal protection required both catalases, as the survival of a double mutant lacking both CatB and CatP was lower than that of single-catalase-deficient cells. Although CatB contributed to reactive oxygen species defensesin vitro, CatB was dispensable for lung infection and extrapulmonary disseminationin vivo. Loss of CatB from a strain also lacking superoxide dismutase (Sod3) did not further reduce the survival ofHistoplasmayeasts. Nevertheless, some catalase function was required for pathogenesis since simultaneous loss of both CatB and CatP attenuatedHistoplasmavirulencein vivo. These results demonstrate thatHistoplasma's dual catalases comprise a system that enablesHistoplasmato efficiently overcome the reactive oxygen produced by the innate immune system.

scholarly journals Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

2017 ◽  
Author(s):  
Grant C. O’Connell ◽  
Connie S. Tennant ◽  
Noelle Lucke-Wold ◽  
Yasser Kabbani ◽  
Abdul R. Tarabishy ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Immune System ◽  
Innate Immune System ◽  
Healthy Donor ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Stroke Patients ◽  
Adaptive Immune ◽  
Soluble Cd163

AbstractCD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

In Vitro Modulation of E. coli Community Behavior and Human Innate Immune System by Lantibiotic Nisin

2012 ◽  
Vol 18 (3) ◽  
pp. 171-183 ◽  
Author(s):  
Deovrat N. Begde ◽  
Sunita B. Bundale ◽  
Mashitha V. Pise ◽  
Jaishree A. Rudra ◽  
Nandita A. Nashikkar ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
E Coli ◽  
Community Behavior

In vitro anti-inflammatory activity of carvacrol: Inhibitory effect on COX-2 catalyzed prostaglandin E2 biosynthesisb

2009 ◽  
Vol 32 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Premysl Landa ◽  
Ladislav Kokoska ◽  
Marie Pribylova ◽  
Tomas Vanek ◽  
Petr Marsik
Keyword(s):  
Prostaglandin E2 ◽  
Inhibitory Effect ◽  
Inflammatory Activity ◽  
Cox 2 ◽  
Anti Inflammatory

scholarly journals Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

2007 ◽  
Vol 57 (1) ◽  
pp. 13-30 ◽  
Author(s):  
Mange Yadav ◽  
Shrikant Shirude ◽  
Devendra Puntambekar ◽  
Pinkal Patel ◽  
Hetal Prajapati ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

Studies in 3,4-diaryl-1,2,5-oxadiazoles and theirN-oxides: Search for better COX-2 inhibitorsA series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazoleN-oxides were prepared and evaluated for COX-2 and COX-1 binding affinityin vitroand for anti-inflammatory activity by the rat paw edema method.p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazoleN-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1and COX-1 enzyme inhibition of 44% at 88 μmol L-1concentrations, but showed very lowin vivoanti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, markedin vivoanti-inflammatory activity (71% at 25 mg kg-1)vs.celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest thatp-methoxy (p-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/N-oxides.

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