Tumor necrosis factor alpha and interleukin-1beta stimulate the expression of cyclooxygenase II but do not alter prostaglandin E2 receptor mRNA levels in cultured dorsal root ganglia cells.
Pain
; 113(1-2): 113-22, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15621371
ABSTRACT
Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) are pro-inflammatory cytokines capable of altering the sensitivity of sensory neurons. Because sensitization elicited by IL-1beta and TNFalpha is blocked by inhibition of the inducible enzyme, cyclooxygenase-II (COX-2), we examined whether these cytokines could increase COX-2 expression in dorsal root ganglion (DRG) cultures. Treatment of cell cultures with either IL-1beta or TNFalpha increases immunoreactive COX-2, as measured by immunoblotting, in a time- and concentration-dependent manner. A 24-h pretreatment with 10 ng/ml IL-1beta or 50 ng/ml TNFalpha augmented COX-2 expression 50- and 8-fold over basal levels, respectively. Immunohistochemistry established the presence of COX-2-like immunoreactivity in both neuronal and non-neuronal cells in culture. The addition of IL-1 receptor antagonist blocked the induction of COX-2 expression by IL-1beta, but did not alter TNFalpha-stimulated increases in COX-2, indicating that the mechanism of TNFalpha is not limited to increasing the expression of IL-1beta. The basal and TNFalpha-induced expression of COX-2 was not dependent on the presence of NGF in the growth media. IL-1beta and TNFalpha treatment for 24 h enhanced prostaglandin E2 (PGE2) production 2-4-fold, which was blocked by pretreatment with the COX-2 inhibitor, NS-398. Exposing cultures to PGE2, IL-1beta, or TNFalpha for 24 h did not alter PGE2 receptor (EP) mRNA levels. These results indicate that TNFalpha and IL-1beta induce the functional expression of COX-2 but not EP receptors in DRG cells in culture and suggest that cytokine-induced sensitization of sensory neurons is secondary to prostaglandin production and not alterations in EP receptors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Interleucina-1
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Fator de Necrose Tumoral alfa
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Prostaglandina-Endoperóxido Sintases
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Gânglios Espinais
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article