scholarly journals Novel Biphasic Role of Resolvin D1 on Expression of Cyclooxygenase-2 in Lipopolysaccharide-Stimulated Lung Fibroblasts Is Partly through PI3K/AKT and ERK2 Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Derong Wu ◽  
Shengxing Zheng ◽  
Wenjuan Li ◽  
Li Yang ◽  
Yongjian Liu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Fibroblasts ◽  
Acute Injury ◽  
Signalling Pathways ◽  
Resolvin D1 ◽  
Cox 2 ◽  
Inflammation Resolution ◽  
Second Peak ◽  
Cox 1

Fibroblasts, far frombeing merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous “braking signal,” resolvins possess potent anti-inflammatory and proresolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2levels also peaked at 6 hours, and PGD2levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimotoʼs Thyroiditis

2021 ◽  
Author(s):  
Jing Song ◽  
Rongxin Sun ◽  
Yuanyuan Zhang ◽  
Ying Fu ◽  
Dong Zhao
Keyword(s):  
Thyroid Autoimmunity ◽  
Thyroid Stimulating Hormone ◽  
Inflammatory Factors ◽  
Thyroid Peroxidase ◽  
Sensitivity Index ◽  
Resolvin D1 ◽  
Thyroid Peroxidase Antibody ◽  
Thyroglobulin Antibody ◽  
Inflammation Resolution

Abstract Objective Resolvins are produced by the catabolism of polyunsaturated fatty acids (PUFAs) and play vital roles in inflammation resolution. Resolvins have been associated with autoimmune disorders. This study aimed to measure the level of Resolvin D1 (RVD1) in the serum of Hashimoto's thyroiditis (HT) patients and healthy controls (HCs) and to further analyse its correlation with thyroid autoantibodies and inflammatory factors. Methods Sixty-three participants were recruited, namely, 30 untreated HT patients and 33 sex- and age-matched HCs. Serum RVD1 and inflammatory chemokine (MCP-1 and IP-10) levels were measured by ELISA according to the manufacturer’s protocol. Serum total T3 (TT3), TT4, free T3 (FT3), FT4, thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and thyroid-stimulating hormone (TSH) levels were measured using an electrochemiluminescence immunoassay. Thyroid homeostasis parameters, including the thyroid secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated. Results Serum RVD1 levels in HT patients (134.76, 85.35–201.36 pg/mL) were significantly lower than those in HCs (187.64, 131.01–326.85 pg/mL) (P=0.004). As the TPOAb level increased, the RVD1 level showed a decreasing trend (P for trend=0.002). Both multinomial and ordinal logistics analyses revealed that serum RVD1 levels were negatively correlated with TPOAb levels in the adjusted models. Moreover, RVD1 showed a negative correlation with the inflammatory chemokine IP-1 0 (r=–0.276, P=0.034), TSHI (r=–0.269, P=0.036) and TTSI (r=–0.277, P=0.031). Conclusions Thyroid autoimmunity may be associated with low levels of RVD1. Decreased RVD1 levels indicate impaired resolution of inflammation in HT patients.

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.

scholarly journals Protection Effect of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Piroxicam as Ulcerogenic Agent towards Malondialdehid Level and Protein Expression of Caspase-3, COX-1, COX-2 at Rat Gastric

2020 ◽  
pp. 273-283
Author(s):  
Iis Wahyuningsih ◽  
Kurnia Ambarwati ◽  
Erninda Ayu Hapsari ◽  
Afifah Fauziyyah ◽  
Azis Ikhsanudin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Expression ◽  
Drug Delivery System ◽  
Delivery System ◽  
Caspase 3 ◽  
Thiobarbituric Acid Reactive Substance ◽  
Sprague Dawley ◽  
Protection Effect ◽  
Cox 2 ◽  
Cox 1

The aim of this study was to determine the protection effect of SNEDDS piroxicam ulcerogenic agent against malondialdehyde (MDA) level and protein expression of caspase-3, COX-1, COX-2. The research was conducted using the test animals as much as 30 male white Sprague dawley (SD) rats aged 1-2 months with a weight of 100-200 grams divided into 5 groups. Treatment was given for 28 days orally. On the 29th day blood samples were also taken for the determination of MDA (Malondialdehid) levels by Thiobarbituric Acid Reactive Substance (TBARs) method using a visible spectrophotometer. Rats were sacrificed, then gastric organs were taken for immunohistochemical testing of caspase-3 and COX-1 expression, COX-2. The statistical analysis showed that the piroxicam SNEDDS group and the piroxicam suspension group decreased expression of the caspase-3 protein, increased COX-1 expression, decreased COX-2 and significantly decreased MDA levels. The piroxicam-containing SNEDDS (Self-Nanoemulsifying Drug Delivery System) form has protection against ulcogenic piroxicam.

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

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.

The role of microRNA in the response to cisplatin treatment

2012 ◽  
Vol 40 (4) ◽  
pp. 821-825 ◽  
Author(s):  
Ross M. Drayton
Keyword(s):  
Protein Expression ◽  
Cisplatin Resistance ◽  
Microrna Expression ◽  
Signalling Pathways ◽  
Cytotoxic Effects ◽  
Cellular Processes

Resistance to the cytotoxic effects of cisplatin can be mediated through changes in a wide variety of cellular processes and signalling pathways. The discovery of microRNAs as regulators of protein expression through the targeting of mRNA has led to a number of studies on the effect of cisplatin treatment on microRNA expression, and the ability of microRNAs to modulate cisplatin resistance.

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 COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla

2014 ◽  
Vol 307 (1) ◽  
pp. F25-F32 ◽  
Author(s):  
Fei Wang ◽  
Xiaohan Lu ◽  
Kexin Peng ◽  
Li Zhou ◽  
Chunling Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Renal Medulla ◽  
Receptor Expression ◽  
Ang Ii ◽  
Cox 2 ◽  
Renin Content

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.

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