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1.
Neurosci Lett ; 694: 215-219, 2019 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-30528878

RESUMO

Synergistic expression of cyclooxygenase-2 (COX-2) by interleukin-1ß (IL-1ß) and bradykinin (BK) in peri-sensory neurons results in the production of prostanoids, which affects sensory neuronal activity and responsiveness and causes hyperalgesia. To evaluate the effects of pro-inflammatory mediators on COX-2 expression, cultured rat dorsal root ganglion (DRG) cells were treated with IL-1ß and BK, which caused persistent increased COX-2 expression. Co-treatment increased COX-2 transcriptional activities in an additive manner by a COX-2 promoter luciferase assay. Immunoprecipitated HuR, an RNA-binding protein, in co-treated DRG cells contained more COX-2 mRNA than that of the control. The synergistic effects of IL-1ß and BK on COX-2 expression may be a result of RNA stabilization mediated by HuR in peri-sensory neurons. Multiple pro-inflammatory cytokines and mediators are produced during neurogenic inflammation and aberrant control of COX-2 mRNA turnover may be implicated in diseases including chronic inflammation, which results in inflammation-derived hyperalgesia around primary sensory neurons.


Assuntos
Bradicinina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Gânglios Espinais/enzimologia , Interleucina-1beta/metabolismo , Animais , Bradicinina/administração & dosagem , Células Cultivadas , Gânglios Espinais/efeitos dos fármacos , Interleucina-1beta/administração & dosagem , Masculino , RNA Mensageiro/metabolismo , Ratos Wistar
2.
Biochem Biophys Res Commun ; 467(2): 367-72, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26431871

RESUMO

The wnt protein family has important members involved in cell differentiation, proliferation and plasticity expression; however, little is known about its biosynthesis processes. On the other hand, an increase in the intracerebral cyclic adenosine 3', 5'-monophosphate (cAMP) level leads to synaptic plasticity via the de novo synthesis of any protein. Here, the effect of dibutyryl cAMP (dbcAMP), a membrane permeability cAMP analog, on the wnt family was investigated in rat primary-cultured glial cells containing astrocytes and microglia. Among wnt3a, 4, 5a, 7a and 11 mRNA, only wnt4 expression was increased by longer treatment (24 h), compared with short treatment (2 h), with dbcAMP in a concentration-dependent manner, and its effect reached statistical significance at 1 mM. In cultures of isolated astrocytes or microglia, wnt4 expression was not affected by 1 mM dbcAMP for 24 h, and microglial wnt4 protein was undetectable even when cells were treated with the drug. Mixed glial cells treated for 24 h with 1 mM dbcAMP showed significantly increased wnt4 protein, as well as mRNA. Immunofluorescence manifested that cells that expressed wnt4 protein were astrocytes, but not microglia. Intraperitoneal injection of 1.25 mg/kg rolipram, a phosphodiesterase (PDE) IV inhibitor that can pass through the blood brain barrier and inhibits cAMP degradation specifically, showed a tendency to increase wnt4 expression in the adult rat brain after 24 h, and the increases in wnt4 mRNA and protein levels reached statistical significance in the hippocampus and striatum, respectively. This is the first finding to help elucidate the selective biosynthesis of central wnt4 through cAMP-stimulated microglia and astrocytes interaction.


Assuntos
Astrócitos/efeitos dos fármacos , Bucladesina/farmacologia , Microglia/efeitos dos fármacos , Proteína Wnt4/agonistas , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Astrócitos/metabolismo , Bucladesina/metabolismo , Comunicação Celular/efeitos dos fármacos , Técnicas de Cocultura , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Injeções Intraperitoneais , Microglia/citologia , Microglia/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Rolipram/farmacologia , Transdução de Sinais , Proteína Wnt4/genética , Proteína Wnt4/metabolismo
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