The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2).
Cell Signal
; 17(4): 525-33, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15601629
ABSTRACT
The mast cell product tryptase, via protease-activated receptor 2 (PAR2), induces cyclooxygenase-2 (COX2) and 15-deoxy-prostaglandin J2 (15d-PGJ2) synthesis. 15d-PGJ2, through the nuclear peroxisome proliferator activated receptor gamma (PPARgamma), subsequently causes fibroblast proliferation. In this study we attempted to determine initial events of the tryptase/PAR2 signaling pathway leading to COX2 induction and fibroblast proliferation. In human fibroblasts (HFFF2), cDNA array, RT-PCR and Western blotting studies demonstrated that tryptase, but not 15d-PGJ2, up-regulates c-jun, c-fos and COX2 expression, and phosphorylates the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Furthermore, tryptase effects on erk1/2, c-jun, c-fos, COX2 and cell proliferation were prevented by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK). Other kinases [P38, stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JUNK), erk5], intracellular Ca(2+) or cAMP were not affected by tryptase/PAR2. Our study identifies crucial intracellular events leading to induction of COX2 and fibroblast proliferation, i.e. a cornerstone of fibrosis.
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Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Prostaglandina-Endoperóxido Sintases
/
Proteína Quinase 1 Ativada por Mitógeno
/
Proteína Quinase 3 Ativada por Mitógeno
/
Fibroblastos
/
Mastócitos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article