Urocortin induces interleukin-6 gene expression via cyclooxygenase-2 activity in aortic smooth muscle cells.
Endocrinology
; 147(9): 4454-62, 2006 Sep.
Article
en En
| MEDLINE
| ID: mdl-16777977
ABSTRACT
Corticotropin-releasing factor (CRF) plays a central role in controlling stress-related activity of the hypothalamic-pituitary-adrenal axis. Four CRF-related peptides have been found in mammals CRF and urocortins (Ucns) 1-3. Ucns bound to CRF(2beta) receptors have a physiological role in the cardiovascular system. We previously found that both Ucn1 and -2 induced accumulation of intracellular cAMP via CRF(2beta) receptor binding and significantly increased IL-6 secretion by A7r5 aortic smooth muscle cells. In the present study, we investigated Ucn effects on IL-6 gene expression and IL-6 synthesis in A7r5 aortic smooth muscle cells. Ucn1 and -2 stimulated IL-6 gene transcription and IL-6 secretion via CRF(2) receptors. Indomethacin, a cyclooxygenase (COX) inhibitor, suppressed IL-6 gene transcription and IL-6 secretion by Ucn1 or -2. NS-398, a COX-2 inhibitor, suppressed IL-6 induction to the same extent as indomethacin. These results suggest that the COX-2 pathway is involved downstream in regulation of Ucn-increased IL-6 gene expression and IL-6 secretion. In addition, COX-2 expression levels were increased at 6 h with the combination of Ucn1 and IL-1, compared with single peptide activation. Ucn1 showed a potent stimulatory effect on IL-6 output, whereas IL-1 alone had no significant effects. However, when Ucn1 was simultaneously used with IL-1, it markedly potentiated the increments in IL-6 output and promoter activity produced by Ucn1. Taken together, these findings indicate that the COX-2 pathway plays a major role in increasing IL-6 levels stimulated by Ucn and IL-1 in A7r5 cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hormona Liberadora de Corticotropina
/
Expresión Génica
/
Interleucina-6
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Ciclooxigenasa 2
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Músculo Liso Vascular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Endocrinology
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón