AChE and RACK1 promote the anti-inflammatory properties of fluoxetine.
J Mol Neurosci
; 53(3): 306-15, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24258317
ABSTRACT
Selective serotonin reuptake inhibitors (SSRIs) show anti-inflammatory effects, suggesting a possible interaction with both Toll-like-receptor 4 (TLR4) responses and cholinergic signaling through as yet unclear molecular mechanism(s). Our results of structural modeling support the concept that the antidepressant fluoxetine physically interacts with the TLR4-myeloid differentiation factor-2 complex at the same site as bacterial lipopolysaccharide (LPS). We also demonstrate reduced LPS-induced pro-inflammatory interleukin-6 and tumor necrosis factor alpha in human peripheral blood mononuclear cells preincubated with fluoxetine. Furthermore, we show that fluoxetine intercepts the LPS-induced decreases in intracellular acetylcholinesterase (AChE-S) and that AChE-S interacts with the nuclear factor kappa B (NFκB)-activating intracellular receptor for activated C kinase 1 (RACK1). This interaction may prevent NFκB activation by residual RACK1 and its interacting protein kinase PKCßII. Our findings attribute the anti-inflammatory properties of SSRI to surface membrane interference with leukocyte TLR4 activation accompanied by intracellular limitation of pathogen-inducible changes in AChE-S, RACK1, and PKCßII.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
/
Fluoxetina
/
Inibidores Seletivos de Recaptação de Serotonina
/
Receptores de Superfície Celular
/
Proteínas de Ligação ao GTP
/
Anti-Inflamatórios
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Mol Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Israel