Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 495-499 ◽  
Author(s):  
George Asimakopoulos ◽  
Kenneth M Taylor ◽  
Dorian O Haskard ◽  
R Clive Landis
Keyword(s):  
Endothelial Cell ◽  
Venous Blood ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Cell Interaction ◽  
Dose Dependent Fashion ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Action ◽  
Inflammatory Effect

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion ( p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

Ketoconazole-p Aminobenzoic Cocrystal Exhibits a Potent Anti-inflammatory Effect on the Skin of BALBc Mice 

2021 ◽  
Author(s):  
Sorina Danescu ◽  
Gabriela Adriana Filip ◽  
Remus Moldovan ◽  
Diana Olteanu ◽  
Andras Nagy ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Parent Drug ◽  
Mouse Ear ◽  
Anti Inflammatory ◽  
Nfκb Pathway ◽  
Cutaneous Mycosis ◽  
Anti Inflammatory Cytokine ◽  
Global Health Problem ◽  
Inflammatory Action ◽  
Inflammatory Effect

Abstract Fungal infections are a growing global health problem. Therefore, our group has designed and characterized a novel cocrystal formulation starting from ketoconazole and para-amino benzoic acid, named KET-PABA aiming to improve the bioavailability, biocompatibility, and efficiency of the parent drug. The cocrystal showed improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency as compared to ketoconazole. The current study investigated the local possible side effects induced on BALBc mice skin by the application of KET-PABA cocrystal. KET-PABA proved to be safe, without signs of skin sensitization as shown by the mouse ear sensitization test (MEST), or histopathology. KET-PABA induced a potent anti-inflammatory effect through the inhibition of proinflammatory cytokines such as IL1α, IL1β, IL6 and TNFα, and other inflammation promoters such as NRF2, compared to the vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NFκB pathway. Overall, KET-PABA application induced no sensitization, moreover, it induced an anti-inflammatory response. Based on the improved antimycotic effect versus ketoconazole and the anti-inflammatory action, KET-PABA cocrystal has the potential to be an efficient drug in the treatment of cutaneous mycosis.

scholarly journals Erythromycin shortens neutrophil survival by accelerating apoptosis.

1995 ◽  
Vol 39 (4) ◽  
pp. 872-877 ◽  
Author(s):  
K Aoshiba ◽  
A Nagai ◽  
K Konno
Keyword(s):  
Inflammatory Diseases ◽  
Clinical Effectiveness ◽  
Maximum Effect ◽  
Intracellular Camp ◽  
Diffuse Panbronchiolitis ◽  
Dose Dependent Fashion ◽  
Anti Inflammatory ◽  
Neutrophil Survival ◽  
Camp Levels ◽  
Inflammatory Action

Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To evaluate the anti-inflammatory action of erythromycin, we examined the survival of isolated neutrophils with and without erythromycin. Erythromycin shortened neutrophil survival in a dose-dependent fashion, with a maximum effect at 10 micrograms/ml [corrected] and above. Survival at 24 h was 63.4% in medium with 10 micrograms of erythromycin per ml compared with 82.7% in control medium (P < 0.01). This shortening of survival was brought about by acceleration of apoptosis, as evidenced by transmission electron microscopy. In a manner similar to that of erythromycin, other macrolide antibiotics, i.e., clarithromycin, roxithromycin, and midecamycin, also shortened neutrophil survival, but neither the beta-lactams ampicillin and cefazolin nor the aminoglycoside gentamicin affected their survival. Erythromycin increased intracellular levels of cyclic AMP (cAMP) to 150% of control levels in neutrophils. Forskolin, rolipram, and dibutyryl-cAMP, which are known to increase intracellular cAMP levels, also shortened neutrophil survival. H-89, an inhibitor of cAMP-dependent protein kinase A, partially blocked the survival-shortening effect of erythromycin. Our findings suggest that erythromycin shortens neutrophil survival at least in part through elevation of intracellular cAMP levels.

Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

1989 ◽  
Vol 257 (6) ◽  
pp. L373-L378 ◽  
Author(s):  
T. Sasaki ◽  
S. Shimura ◽  
K. Ikeda ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Submucosal Gland ◽  
Thromboxane Receptor ◽  
Significant Stimulation ◽  
Submucosal Glands ◽  
Dose Dependent Fashion ◽  
Thromboxane Receptor Antagonist ◽  
Dose Dependent ◽  
Thromboxane A2 Analogue

Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation.

scholarly journals Anti-Inflammatory Effect of Feiyangchangweiyan Capsule on Rat Pelvic Inflammatory Disease through JNK/NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Yao Li ◽  
Yang Liu ◽  
Qian Yang ◽  
Zhihui Shi ◽  
Yanhua Xie ◽  
...  
Keyword(s):  
Pelvic Inflammatory Disease ◽  
Inflammatory Disease ◽  
Genital Tract ◽  
Nuclear Translocation ◽  
Immunohistochemical Analysis ◽  
Dependent Manner ◽  
Preventive Effect ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Effect

Objectives. In this study, we aimed to illustrate the preventive effect and possible mechanisms of Feiyangchangweiyan capsule (FYCWYC) on rat pelvic inflammatory disease (PID) model. Methods. To construct the rat PID model, upper genital tract was infected by multipathogen, and then drugs were orally administered for 8 days. The histological examination, immunohistochemical analysis, and ELISA were carried out. Furthermore, Western blotting was used to analyze the expression of Akt, MAPKs, NF-κB p65, and IκB-α in uterus. Results. As the results showed, infiltrations of neutrophils and lymphocytes in uterus were significantly suppressed, and IL-1β, IL-6, CXCL-1, and TNF-α were also reduced in a dose-dependent manner. We also found that FYCWYC inhibited apoptosis induced by infection. Furthermore, FYCWYC could block the infection-induced nuclear translocation of NF-κB. We found that FYCWYC treatment only decreased the phosphorylation of JNK induced by infection and had no effects on Akt and P38. Additional, the effects of SP600125, an inhibitor of phospho-JNK, were similar to the results of FYCWYC. Conclusions. Taken together, our results demonstrated that FYCWYC had anti-inflammatory effect in pathogen-induced PID model, and the mechanism might be through inhibiting NF-κB nuclear translocation which is mediated by JNK.

scholarly journals Histamine induces interleukin-8 secretion by endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2229-2233 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
P Gosset ◽  
S Molet ◽  
P Lassalle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Histamine Receptor ◽  
Leukotriene B4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Delayed Effects ◽  
Allergic Disorders ◽  
Dose Dependent

It has been shown that histamine induces early changes on endothelial cells (EC), such as a transient expression of P-selectin and secretion and/or surface expression of early mediators (eg, prostacyclin [PG1(2)], platelet-activating factor [PAF], and leukotriene B4 [LTB4]). However, delayed effects of histamine on EC and particularly on cytokine production are undefined. In this study, the effect of histamine on interleukin (IL)-8 production by EC was evaluated using an enzyme-linked immunosorbent assay (ELISA) method and mRNA expression. The results showed that histamine increased the secretion and the mRNA expression of IL-8 by EC. Histamine-induced IL-8 production was (1) dose-dependent (at a dose > or = 10(-6) mol/L), (2) potentialized by costimulation with tumor necrosis factor (TNF)-alpha, (3) inhibited by H1 or H2 histamine receptor antagonists, and (4) significantly increased 4 hours after the initial stimulation. These data suggest that histamine may be involved in the control of the late inflammatory reaction associated to allergic disorders through IL-8 secretion by EC.

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