RT Journal Article
T1 AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity.
A1 Saliba, Soraya Wilke
A1 Marcotegui, Ariel R
A1 Fortwängler, Ellen
A1 Ditrich, Johannes
A1 Perazzo, Juan Carlos
A1 Muñoz, Eduardo
A1 de Oliveira, Antônio Carlos Pinheiro
A1 Fiebich, Bernd L
K1 AM404
K1 Acetaminophen
K1 Cyclooxygenase
K1 Inflammation
K1 Microglia
K1 Prostaglandins
AB N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA. Our results show that AM404 inhibited LPS-mediated prostaglandin E2 (PGE2) production in OHSC, and LPS-stimulated PGE2 release was totally abolished in OHSC if microglial cells were removed. In primary microglia cultures, AM404 led to a significant dose-dependent decrease in the release of PGE2, independent of TRPV1 or CB1 receptors. Moreover, AM404 also inhibited the production of PGD2 and the formation of reactive oxygen species (8-iso-PGF2 alpha) with a reversible reduction of COX-1- and COX-2 activity. Also, it slightly decreased the levels of LPS-induced COX-2 protein, although no effect was observed on LPS-induced mPGES-1 protein synthesis. This study provides new significant insights about the potential anti-inflammatory role of AM404 and new mechanisms of action of paracetamol on the modulation of prostaglandin production by activated microglia.
PB BioMed Central
YR 2017
FD 2017-12-27
LK http://hdl.handle.net/10668/11903
UL http://hdl.handle.net/10668/11903
LA en
NO Saliba SW, Marcotegui AR, Fortwängler E, Ditrich J, Perazzo JC, Muñoz E, et al.  AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity. J Neuroinflammation. 2017 Dec 13;14(1):246. doi: 10.1186/s12974-017-1014-3. Erratum in: J Neuroinflammation. 2018 Feb 6;15(1):34
DS RISalud
RD Apr 5, 2025