Triazol-phenyl antipyretic derivatives inhibit mPGES-1 mRNA levels in LPS-Induced RAW 264.7 macrophage cells

2020 ◽  
Vol 19 ◽  
Author(s):  
Lenisa Dandara dos Santos ◽  
Thamires Quadros Froes ◽  
Miriam Cristina Contin de Melo ◽  
Gloria Emília Petto de Souza ◽  
Denis de Melo Soares ◽  
...  
Keyword(s):  
Comparable Efficacy ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Febrile Response ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Pge2 Concentration ◽  
Raw 264.7 Macrophage Cells ◽  
Cox 2

Background:: Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) production, which plays an important role in the regulation of febrile response. In our previous work, ligand-based pharmacophore models, built with mPGES-1 inhibitors, were employed to identify a novel series of compounds that reduce the febrile response in rats. Objectives:: Evaluate the mechanism of action of the most active compound (1). Methods:: For in vivo assays, rats were pretreated with the antipyretic compounds 1-8, 30 min before LPS injection. For in vitro assays, RAW 264.7 macrophage cells were incubated with the antipyretic compounds 1-8 for 1 hour before LPS stimu-lus. After 16 h, quantitative real-time PCR was carried out. Additionally, the PGE2 concentration in hypothalamus was quantified by ELISA and the inhibitory effect of N-cyclopentyl-N'-[3-(3-cyclopropyl-1H-1,2,4-triazol-5-yl)phenyl]ethanediamide (1) over human COX-2 enzymatic activity was determined with a COX Colorimetric Inhibitor Screening Assay Kit. Results:: Compound 1 and CAY10526 have comparable efficacy to reduce the febrile response when injected i.v. (com-pound 1: 63.10%, CAY10526: 70.20%). Moreover, compound 1 significantly reduces the mPGES-1 mRNA levels, in RAW264.7 cells, under inflammatory conditions. A chemically-similar compound (8- ) also significantly reduces the mRNA levels of the gene target. On the other hand, compounds 6 and 7, which are also somewhat similar to compound 1, do not, significantly, impact mPGES-1 mRNA levels. Conclusions:: PGE2 concentration reduction in hypothalamus, due to compound 1 central injection, is related to decreased mPGES-1 mRNA levels but not to COX-2 inhibition (IC50> 50 μM). Therefore, compound 1 is a promising lead for inno-vative antipyretic drug development.

scholarly journals Inhibition of LPS-Induced iNOS, COX-2 and Cytokines Expression by Poncirin through the NF-κB Inactivation in RAW 264.7 Macrophage Cells

2007 ◽  
Vol 30 (12) ◽  
pp. 2345-2351 ◽  
Author(s):  
Jong-Bin Kim ◽  
Ah-Reum Han ◽  
Eun-Young Park ◽  
Ji-Yeon Kim ◽  
Woong Cho ◽  
...  
Keyword(s):  
Raw 264.7 ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Raw 264.7 Macrophage Cells ◽  
Cox 2

scholarly journals Citrus unshiu flower inhibits LPS-induced iNOS and COX-2 via MAPKs in RAW 264.7 macrophage cells

2015 ◽  
Vol 31 (4) ◽  
pp. 1915-1922 ◽  
Author(s):  
Min-Jin Kim ◽  
Kyong-Wol Yang ◽  
Eun-Jin Yang ◽  
Sang Kim ◽  
Kyung Park ◽  
...  
Keyword(s):  
Raw 264.7 ◽  
Citrus Unshiu ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Raw 264.7 Macrophage Cells ◽  
Cox 2

scholarly journals Composition and Acute Inflammatory Response from Tetraponera rufonigra Venom on RAW 264.7 Macrophage Cells

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 257
Author(s):  
Suwatjanee Naephrai ◽  
Supakit Khacha-ananda ◽  
Pornsiri Pitchakarn ◽  
Churdsak Jaikang
Keyword(s):  
Protein Composition ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Crude Venom ◽  
Venom Protein ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Ant Venom ◽  
Raw 264.7 Macrophage Cells ◽  
Cox 2

Tetraponera rufonigra (Arboreal Bicoloured Ant) venom induces pain, inflammation, and anaphylaxis in people and has an increased incident in Southeast Asia regions. The bioactive components and mechanism of action of the ant venom are still limited. The aim of this research was to identify the protein composition and inflammatory process of the ant venom by using RAW 264.7 macrophage cells. The major venom proteins are composed of 5’ nucleotidase, prolyl endopeptidase-like, aminopeptidase N, trypsin-3, venom protein, and phospholipase A2 (PLA2). The venom showed PLA2 activity and represented 0.46 μg of PLA2 bee venom equivalent/μg crude venom protein. The venom induced cytotoxic in a dose- and time-dependent manner with IC20 approximately at 4.01 µg/mL. The increased levels of COX-2 and PGE2 were observed after 1 h of treatment correlating with an upregulation of COX-2 expression. Moreover, the level of mPGES-1 expression was obviously increased after 12 h of venom induction. Hence, our results suggested that the induction of COX-2/mPGEs-1 pathway could be a direct pathway for the ant venom-induced inflammation.

scholarly journals Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells

2011 ◽  
Vol 44 (3) ◽  
pp. 194 ◽  
Author(s):  
Chin-Ok Yi ◽  
Byeong Tak Jeon ◽  
Hyun Joo Shin ◽  
Eun Ae Jeong ◽  
Ki Churl Chang ◽  
...  
Keyword(s):  
Raw 264.7 ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Raw 264.7 Macrophage Cells ◽  
Cox 2

scholarly journals Ethyl ferulate contributes to the inhibition of the inflammatory responses in murine RAW 264.7 macrophage cells and acute lung injury in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251578
Author(s):  
Yu Wang ◽  
Xuan Zhang ◽  
Linger Li ◽  
Zhao Zhang ◽  
Chengxi Wei ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Ethyl Ferulate ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Tnf Α ◽  
Raw 264.7 Macrophage Cells

Background Ethyl ferulate (EF) is a derivative of ferulic acid (FA), which is a monomeric component purified from the traditional medicinal herb Ferula, but its effects have not been clear yet. The purpose of this study was to evaluate whether EF can reduce inflammation levels in macrophages by regulating the Nrf2-HO-1 and NF-кB pathway. Methods The LPS-induced raw 264.7 macrophage cells model was used to determine the anti-inflammatory and anti-oxidative stress effects of EF. The levels of IL-1β, IL-6, TNF-α and PGE2 were analyzed by ELISA. The mRNA and protein of COX-2, iNOS, TNF-α, IL-6, HO-1 and Nrf2 were identified by RT-PCR analysis and western blotting. Intracellular ROS levels were assessed with DCFH oxidation staining. The expressions of NF-кB p-p65 and Nrf2 were analyzed by immunofluorescence assay. The inhibitory effect of Nrf2 inhibitor ML385 (2μM) on mediatation of antioxidant activity by raw 264.7 macrophage cells was evaluated. The effect of EF was confirmed in acute lung injury mice model. Results In our research, EF reduced the expression of iNOS, COX2 and the production of PGE2. EF could inhibit the production of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in lipopolysaccharide (LPS) stimulated macrophages and decreased expression of IL-6 and TNF-α in LPS stimulated macrophages. Furthermore, EF inhibited NF-кB p65 from transporting to the nucleus, decreased the expression of p-IкBα, significantly decreased the level of intracellular reactive oxygen species (ROS) and activated Nrf2/HO-1 pathways. EF could attenuate the degree of leukocyte infiltration, reduced MPO activity, mRNA levels and secretion of TNF-α and IL-6 in vivo. EF exhibited potent protective effects against LPS-induced acute lung injury in mice. Conclusions Collectively, our data showed that EF relieved LPS-induced inflammatory responses by inhibiting NF-κB pathway and activating Nrf2/HO-1 pathway, known to be involved in the regulation of inflammatory responses by Nrf2.

Sign in / Sign up

Export Citation Format

Share Document