2-Carba cyclic phosphatidic acid inhibits lipopolysaccharide-induced prostaglandin E2 production in a human macrophage cell line

Abstract

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator that contains a unique cyclic phosphate ring at the sn -2 and sn -3 positions of its glycerol backbone. Using mouse models for multiple sclerosis (cuprizone-induced demyelination and experimental autoimmune encephalomyelitis) and traumatic brain injury, we revealed that cPA and its metabolically stabilized cPA derivative, 2-carba-cPA (2ccPA), have potential to protect against neuroinflammation. In this study, we investigated whether 2ccPA has anti-inflammatory effect on peripheral immune function or not using inflammation-induced macrophages-like cell line, THP-1 monocytes differentiated by phorbol 12-myristate 13-acetate (PMA). Lipopolysaccharide (LPS)-stimulated THP-1 cells were found to have higher expression of the mRNAs of several inflammation-related cytokines and of the enzyme cyclooxygenase-2 (Cox-2); however, when THP-1 cells were stimulated by LPS in the presence of 2ccPA, the increase in the expression of pro-inflammatory cytokine and Cox-2 mRNA was attenuated. 2ccPA treatment also decreased the amount of prostaglandin E2 (PGE2) produced by LPS-stimulated THP-1 cells and decreased expression of the mRNA of prostaglandin E receptor 2 (EP2, PTGER2 ), a PGE2 receptor that mediates inflammation. These results indicate that 2ccPA has anti-inflammatory properties.

Rational Design and Synthesis of New Selective COX-2 Inhibitors with In Vivo PGE2-Lowering Activity by Tethering Benzenesulfonamide and 1,2,3-Triazole Pharmacophores to Some NSAIDs

“…The quantitative determination of PGE2 in biological fluids was carried out for compounds 6b, 6j and 6e as well as the reference drugs celecoxib and diclofenac according to the competitive immunoassay procedure, as previously reported [ 42 ] (approved by HU-IACUC) [ 41 ]. For more details, see Page S16, Supplementary File .…”

Endoplasmic reticulum stress inhibits adipocyte differentiation of mesenchymal stem cells

“…To quantify the mRNA levels of the genes of interest, qRT-PCR was performed using the NEB Luna Universal qPCR master mix (New England Biolabs Japan Inc., Tokyo, Japan) on a LightCycler 96 system (Roche, Tokyo, Japan). Gene-specific primer sets for ILs have been previously described (Shibaike et al 2019). The other primer sets used are listed in Table 1.…”

A Review of Cyclic Phosphatidic Acid and Other Potential Therapeutic Targets for Treating Osteoarthritis

“…Therefore, its ability to protect neurons and potentially mitigate neurodegenerative diseases could be further explored. Some studies have shown the anti-inflammatory properties of 2carba-cPA [113], indicating its potential to modulate immune responses and inflammation-related diseases [114]. Research suggests that 2carba-cPA may play a role in metabolic regulation, including the control of lipid metabolism and glucose homeostasis, which could have implications for the treatment of metabolic disorders like diabetes and obesity.…”