scholarly journals Crotalus durissus ruruima Snake Venom and a Phospholipase A2 Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ana Eduarda Zulim de Carvalho ◽  
Karina Giannotti ◽  
Elbio Leiguez Junior ◽  
Márcio Matsubara ◽  
Maria Cristina Dos Santos ◽  
...  
Keyword(s):  
Snake Venom ◽  
Inflammatory Mediators ◽  
Lipid Droplets ◽  
Lipid Mediators ◽  
Immunological Responses ◽  
Inflammatory Stimuli ◽  
Cox 2 ◽  
Crotalus Durissus ◽  
Cox 1

Viper snake Crotalus durissus ruruima (Cdr) is a subspecies found in northern area of Brazil. Among the snakes of Crotalus genus subspecies, the venom of Cdr presents highest level of crotoxin, which is the major component of Crotalus snake venoms, formed by two subunits (crotapotin and a phospholipase A2 named CBr) and presents potent neurotoxic activity. Curiously, the venom of C. d. ruruima (CdrV) is better neutralized by antibothropic than by anticrotalic serum, strongly suggesting that this venom has similarities with venom of Bothrops genus snakes with regard to the ability to induce inflammation. Macrophages are cells with a central role in inflammatory and immunological responses. Upon inflammatory stimuli, these cells exhibit increased numbers of lipid droplets, which are key organelles in the synthesis and release of inflammatory mediators. However, the effects of CdrV and CBr in macrophage functions are unknown. We herein investigated the ability of CdrV and CBr to activate macrophages with focus on the formation of lipid droplets (LDs), synthesis of lipid mediators, and mechanisms involved in these effects. The involvement of LDs in PGE2 biosynthesis was also assessed. Stimulation of murine macrophages with CdrV and CBr induced an increased number of LDs and release of prostanoids (PGE2, PGD2, and TXB2). Neither CdrV nor CBr induced the expression of COX-1 and COX-2 by macrophages. LDs induced by both CdrV and CBr are associated to PLIN2 recruitment and expression and were shown to be dependent on COX-1, but not COX-2 activity. Moreover, PGE2 colocalized to CdrV- and CBr-induced LDs, revealing the role of these organelles as sites for the synthesis of prostanoids. These results evidence, for the first time, the ability of a whole snake venom to induce formation of LDs and the potential role of these organelles for the production of inflammatory mediators during envenomation by Crotalus snakes.

The role of prostaglandins and Cyclooxygenase in pathogenesis of chronic endometritis

2017 ◽  
pp. 98-100
Author(s):  
Е.И. Самоделкин ◽  
Н.Г. Меркучева ◽  
П.В. Косарева ◽  
Л.Ю. Нестерова
Keyword(s):  
Inflammatory Cytokine ◽  
Inflammatory Process ◽  
Lipid Mediators ◽  
Reproductive Age ◽  
Physiological Functions ◽  
Chronic Endometritis ◽  
Pathogenetic Therapy ◽  
Cox 2 ◽  
Cox 1

Цель обзора - представить современные данные о роли циклооксигеназ (СОХ) в развитии хронического эндометрита. Проанализировано 106 источников литературы, посвященных роли COX-1 и COX-2 в развитии хронического эндометрита у пациенток репродуктивного возраста, опубликованных в базах данных Medline, Pubmed, Scopus, из них 14 включены в настоящий обзор. В поддержании воспалительного процесса в эндометрии важная роль отводится простагландинам (PG). Тем не менее, продукция PG и лейкотриенов (LTS) - липидных медиаторов, которые наряду с PG играют основную роль в воспалительном процессе, в воспаленной матке до конца не изучена. Циклооксигеназа-2 - фермент, обладающий разнообразными физиологическими функциями, участвует и в репродукции, роль его в которой многогранна. К настоящему времени установлено, что ингибирование циклооксигеназных путей, блокирующее синтез простагландинов, нивелирует эффекты многих провоспалительных цитокинов, участвующих в патогенезе хронического эндометрита. Заключение. Вопрос о роли циклооксигеназ в развитии хронического эндометрита интересен тем, что на основании полученных знаний можно планировать применение препаратов, ингибирующих циклооксигеназные пути (нестероидных противовоспалительных препаратов) при лечении хронического эндометрита - как способа патогенетически обоснованной терапии. Вопрос до конца не изучен. Необходимы дальнейшие исследования в этой области. The purpose: to present the modern data of cyclooxygenase role (COX) in the development of chronic endometritis.106 references on the role of COX-1 and COX-2 in the development of chronic endometritis in patients of reproductive age, published in the Medline database, Pubmed, Scopus were analyzed; 14 sources are included in this review. Prostaglandins (PG) play an important role in maintaining inflammatory process in the endometrium. Nevertheless, the production of PG and leukotrienes (LTS) - lipid mediators, which, along with PG, play a major role in the inflammatory process of the inflamed uterus, is not fully understood. Cyclooxygenase-2, the enzyme having various physiological functions, is involved in reproduction, where its role is polyfunctional. It has been established that the inhibition of cyclooxygenase pathways, blocking the synthesis of prostaglandins, eliminates the effects of many pro-inflammatory cytokine involved in the pathogenesis of chronic endometritis. Conclusion. The role of cyclooxygenase in the development of chronic endometritis is interesting; on the basis of the acquired knowledge, we can plan the use of drugs that inhibit the cyclooxygenase pathway (NSAIDs) in the treatment of chronic endometritis - as a method of pathogenetic therapy. The issue is not fully understood. Further research is needed in this sphere.

Functional Morphology of Thecal Glands in the Ovary of Japanese Quails (Coturnix japonica)

2018 ◽  
Vol 205 (1) ◽  
pp. 32-41
Author(s):  
Daniela Rodler ◽  
Fred Sinowatz
Keyword(s):  
Lipid Droplets ◽  
Smooth Endoplasmic Reticulum ◽  
Cell Types ◽  
Coturnix Japonica ◽  
Ultrastructural Studies ◽  
Japanese Quails ◽  
Transmission Electron ◽  
Cox 2 ◽  
Cox 1

The role of thecal glands in the ovary of birds remains controversial. Using transmission electron microscopy and immunohistochemistry, immunohistochemical localisation of cyclooxygenase I and II (COX-1 and COX-2), oestrogen receptor α and β (ER-α and ER-β), androgen receptor (AR) and progesterone receptor (PR), a detailed analysis of the thecal glands was performed. Our ultrastructural studies revealed that the thecal glands of the quail ovary consist of 2 cell types, steroid-producing cells (SPCs) and enclosing cells (ENCs). The SPCs are large, light cells containing a varying number of lipid droplets. Their cytoplasm is characterised by a large amount of smooth endoplasmic reticulum. The ENCs are always located at the periphery of the gland. Some ENCs contain an abundant number of microfilaments, but lipid droplets and dense bodies were rare. Within 1 gland, SPCs with distinct COX-2 immunostaining were interspersed between usually larger numbers of moderately COX-2-positive cells. A completely different staining pattern was observed for COX-1, where the cytoplasm of the ENCs was distinctly immunopositive. The SPCs stained only weakly with antibodies to COX-1. The thecal glands showed distinct reactions for ER-β but only a weak to negative one for ER-α, PR, and AR. Our immunohistochemical and ultrastructural data support our hypothesis that the thecal glands of the quail are involved in steroid hormone and prostaglandin synthesis. The prostaglandins secreted by the thecal glands probably contribute to the ovulation of the follicle first in the hierarchy.

scholarly journals Role of cyclooxygenase isoforms in prostacyclin biosynthesis and murine prehepatic portal hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. G953-G964 ◽  
Author(s):  
N. J. Skill ◽  
N. G. Theodorakis ◽  
Y. N. Wang ◽  
J. M. Wu ◽  
E. M. Redmond ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
The United States ◽  
Portal Vein Ligation ◽  
Wild Type ◽  
Sham Surgery ◽  
Cox 2 ◽  
Hemodynamic Measurements ◽  
Cyclooxygenase Isoforms ◽  
Cox 1

Portal hypertension (PHT) is a common complication of liver cirrhosis and significantly increases morbidity and mortality. Abrogation of PHT using NSAIDs has demonstrated that prostacyclin (PGI2), a direct downstream metabolic product of cyclooxygenase (COX) activity, is an important mediator in the development of experimental and clinical PHT. However, the role of COX isoforms in PGI2 biosynthesis and PHT is not fully understood. Prehepatic PHT was induced by portal vein ligation (PVL) in wild-type, COX-1−/−, and COX-2−/− mice treated with and without COX-2 (NS398) or COX-1 (SC560) inhibitors. Hemodynamic measurements and PGI2 biosynthesis were determined 1–7 days after PVL or sham surgery. Gene deletion or pharmacological inhibition of COX-1 or COX-2 attenuated but did not ameliorate PGI2 biosynthesis after PVL or prevent PHT. In contrast, treatment of COX-1−/− mice with NS398 or COX-2−/− mice with SC560 restricted PGI2 biosynthesis and abrogated the development of PHT following PVL. In conclusion, either COX-1 or COX-2 can mediate elevated PGI2 biosynthesis and the development of experimental prehepatic PHT. Consequently, PGI2 rather then COX-selective drugs are indicated in the treatment of PHT. Identification of additional target sites downstream of COX may benefit the >27,000 patients whom die annually from cirrhosis in the United States alone.

Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

1998 ◽  
Vol 114 ◽  
pp. A82
Author(s):  
T. Brzozowski ◽  
P.C. Konturek ◽  
R. Pajdo ◽  
N. Nagraba ◽  
A. Szczeklik ◽  
...  
Keyword(s):  
Cyclooxygenase 2 ◽  
Mild Stress ◽  
Adaptive Cytoprotection ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

scholarly journals Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation

2018 ◽  
Vol 19 (8) ◽  
pp. 2405 ◽  
Author(s):  
Caroline Costa ◽  
Mariana Belchor ◽  
Caroline Rodrigues ◽  
Daniela Toyama ◽  
Marcos de Oliveira ◽  
...  
Keyword(s):  
Serine Protease ◽  
Snake Venom ◽  
Serine Proteases ◽  
Three Dimensional ◽  
Negative Control ◽  
Protease Activated Receptors ◽  
Crotalus Durissus Terrificus ◽  
Three Dimensional Modeling ◽  
Cox 2 ◽  
Crotalus Durissus

Snake venom serine proteases (SVSPs) represent an essential group of enzymatic toxins involved in several pathophysiological effects on blood homeostasis. Some findings suggest the involvement of this class of enzymatic toxins in inflammation. In this paper, we purified and isolated a new gyroxin isoform from the Crotalus durissus terrificus (Cdt) venom, designated as Cdtsp 2, which showed significant proinflammatory effects in a murine model. In addition, we performed several studies to elucidate the main pathway underlying the edematogenic effect induced by Cdtsp 2. Enzymatic assays and structural analysis (primary structure analysis and three-dimensional modeling) were closely performed with pharmacological assays. The determination of edematogenic activity was performed using Cdtsp 2 isolated from snake venom, and was applied to mice treated with protein kinase C (PKC) inhibitor, phospholipase C (PLC) inhibitor, dexamethasone (Dexa), antagonists for protease-activated receptors (PARs), or saline (negative control). Additionally, we measured the levels of cyclooxygenase 2 (COX-2), malondialdehyde (MDA), and prostaglandin E2 (PGE2). Cdtsp 2 is characterized by an approximate molecular mass of 27 kDa, an isoelectric point (pI) of 4.5, and significant fibrinolytic activity, as well as the ability to hydrolyze Nα-benzoyl-l-arginine 4-nitroanilide (BAPNA). Its primary and three-dimensional structures revealed Cdtsp 2 as a typical snake venom serine protease that induces significant edema via the metabolism of arachidonic acid (AA), involving PARs, PKC, PLC, and COX-2 receptors, as well as inducing a significant increase in MDA levels. Our results showed that Cdtsp 2 is a serine protease with significant enzymatic activity, and it may be involved in the degradation of PAR1 and PAR2, which activate PLC and PKC to mobilize AA, while increasing oxidative stress. In this article, we provide a new perspective for the role of SVSPs beyond their effects on blood homeostasis.

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

2002 ◽  
Vol 283 (4) ◽  
pp. R862-R868 ◽  
Author(s):  
F. Lugarini ◽  
B. J. Hrupka ◽  
G. J. Schwartz ◽  
C. R. Plata-Salaman ◽  
W. Langhans
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclooxygenase 2 ◽  
Major Metabolite ◽  
Time Dependent ◽  
Selective Inhibitors ◽  
Cox 2 ◽  
Cox 1

Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 μg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE2levels after LPS administration. LPS induced a time-dependent increase of PGE2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE2, whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE2 as a potential neuromodulator involved in this response.

COX-2 inhibition prevents downregulation of key renal water and sodium transport proteins in response to bilateral ureteral obstruction

2005 ◽  
Vol 289 (2) ◽  
pp. F322-F333 ◽  
Author(s):  
Rikke Nørregaard ◽  
Boye L. Jensen ◽  
Chunling Li ◽  
Weidong Wang ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Sodium Transport ◽  
Ureteral Obstruction ◽  
Transport Proteins ◽  
Outer Medulla ◽  
Fold Induction ◽  
Cox 2 ◽  
Type 3 ◽  
Sodium Handling ◽  
Cox 1

Bilateral ureteral obstruction (BUO) is associated with marked changes in the expression of renal aquaporins (AQPs) and sodium transport proteins. To examine the role of prostaglandin in this response, we investigated whether 24-h BUO changed the expression of cyclooxygenases (COX-1 and -2) in the kidney and tested the effect of the selective COX-2 inhibitor parecoxib (5 mg·kg−1·day−1 via osmotic minipumps) on AQPs and sodium transport. Sham and BUO kidneys were analyzed by semiquantitative immunoblotting, and a subset of kidneys was perfusion fixed for immunocytochemistry. BUO caused a significant 14-fold induction of inner medullary COX-2 (14.40 ± 1.8 vs. 1.0 ± 0.4, n = 6; P < 0.0001) and a reduction in medullary tissue osmolality, whereas COX-1 did not change. Immunohistochemistry confirmed increased COX-2 labeling associated with medullary interstitial cells. COX isoforms did not change in cortex/outer medulla after 24-h BUO. In BUO kidneys, inner medullary AQP2 expression was reduced, and this decrease was prevented by parecoxib. In the inner stripe of outer medulla, the type 3 Na+/H+ exchanger (NHE3) and apical Na+-K+-2Cl− cotransporter (BSC-1) were significantly reduced by BUO, and this decrease was significantly attenuated by parecoxib. Immunohistochemistry for AQP2, NHE3, and BSC-1 confirmed the effect of parecoxib. Parecoxib had no significant effect on the Na-K-ATPase α1-subunit, type II Na-Pi cotransporter, or AQP3. In conclusion, acute BUO leads to marked upregulation of COX-2 in inner medulla and selective COX-2 inhibition prevents dysregulation of AQP2, BSC-1, and NHE3 in response to BUO. These data indicate that COX-2 may be an important factor contributing to the impaired renal water and sodium handling in response to BUO.

scholarly journals The role of cyclooxygenase inhibitors in lipopolysaccharide-induced hypophagia in chicken

2018 ◽  
Vol 60 (No. 8) ◽  
pp. 342-350 ◽  
Author(s):  
M. Zendehdel ◽  
A. Baghbanzadeh ◽  
B. Yeganeh ◽  
S. Hassanpour
Keyword(s):  
Feed Intake ◽  
Cyclooxygenase Inhibitors ◽  
Post Injection ◽  
Cyclooxygenase Inhibitor ◽  
Guide Cannula ◽  
Treatment Groups ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

Previous studies showed that cyclooxygenase 1 (COX) enzyme has an important role in lipopolysaccharide (LPS)-induced hypophagia in mammals but the effect of COX on LPS-induced hypophagia has not been studied in avian species. The current study was designed to investigate the effects of Indomethacin, a non-selective cyclooxygenase inhibitor, Aspirin (irreversible cyclooxygenase inhibitor), Piroxicam (a selective COX-1 inhibitor), and Celecoxib (a selective COX-2 inhibitor) on LPS-induced hypophagia in 3-h food-deprived (FD<sub>3</sub>) cockerels. One hundred and sixty ROSS 308 chickens were randomly divided into 5 experiments and 4 treatment groups (8 replicates in each group of experiments). Guide cannula was surgically implanted into the lateral ventricle of chickens. In Experiment 1, birds received LPS (5, 10, and 20 ng) intracerebroventricularly (ICV). In Experiment 2, chickens were intraperitoneally (i.p.) injected with Indomethacin (5&nbsp;mg/kg) prior to LPS injection (20 ng; ICV). In Experiment 3, birds were i.p. injected with Aspirin (50 mg/kg) followed by LPS injection (20 ng; ICV). In Experiment 4, chickens were given LPS (20 ng; ICV) after Piroxicam injection (10 mg/kg; i.p.). In Experiment 5, chickens were injected with Celecoxib (10 mg/kg; i.p.) prior to LPS injection (20 ng; ICV). Cumulative feed intake was determined until 8 h post-injection. According to the results, LPS significantly decreased feed intake at 4 and 8 h post injection in birds (P &le; 0.05). Furthermore, LPS-induced hypophagia was attenuated by pre-injection with Indomethacin, Aspirin, and Celecoxib (P&nbsp;&le; 0.05). However, Piroxicam had no effect on LPS-induced hypophagia (P &ge; 0.05). These results suggest that presumably COX-2 mediates LPS-induced hypophagia in broilers.

Sign in / Sign up

Export Citation Format

Share Document