Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Inflammatory Bowel Disease
| ISSN: | 0021-9258 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_________::c1814c99e0327b5c5c07559ccf6710f8 https://doi.org/10.1074/jbc.m312972200 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi...........c1814c99e0327b5c5c07559ccf6710f8 |
| Autor: | Tadashi Tanabe, Hiroaki Naraba, Kenneth D. Glazier, Dragan Golijanin, Andrew J. Dannenberg, Kiron M. Das, Ellen Scherl, Robert A. Soslow, Kazuhiko Yoshimatsu, Kotha Subbaramaiah |
| Rok vydání: | 2004 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty medicine.medical_treatment Guanylate cyclase activity CAAT box Prostaglandin Cell Biology Guanylate cyclase 2C Biology Biochemistry chemistry.chemical_compound Endocrinology Intestinal mucosa chemistry Internal medicine medicine lipids (amino acids peptides and proteins) Protein kinase A Molecular Biology Protein kinase C Prostaglandin E |
| Zdroj: | Journal of Biological Chemistry. 279:12647-12658 |
| ISSN: | 0021-9258 |
| Popis: | Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of cyclooxygenase-derived prostaglandin (PG) H(2) to PGE(2). Increased amounts of mPGES-1 were detected in inflamed intestinal mucosa from patients with inflammatory bowel disease (IBD). Treatment with tumor necrosis factor (TNF)-alpha stimulated mPGES-1 transcription in human colonocytes, resulting in increased amounts of mPGES-1 mRNA and protein. The inductive effect of TNF-alpha localized to the GC box region of the mPGES-1 promoter. Binding of Egr-1 to the GC box region of the mPGES-1 promoter was enhanced by treatment with TNF-alpha. Notably, increased Egr-1 expression and binding activity were also detected in inflamed mucosa from IBD patients. Treatment with TNF-alpha induced the activities of phosphatidylcholine-phospholipase C (PC-PLC) and protein kinase (PK) C and enhanced NO production. A pharmacological approach was used to implicate PC-PLC --> PKC --> NO signaling as being important for the induction of mPGES-1 by TNF-alpha. TNF-alpha also enhanced guanylate cyclase activity and inhibitors of guanylate cyclase activity blocked the induction of mPGES-1 by TNF-alpha. YC-1, an activator of guanylate cyclase, induced mPGES-1. Overexpressing a dominant negative form of PKG blocked TNF-alpha-mediated stimulation of the mPGES-1 promoter. Taken together, these results suggest that overexpression of mPGES-1 in IBD is the result of Egr-1-mediated activation of transcription. Moreover, TNF-alpha induced mPGES-1 by stimulating PC-PLC --> PKC --> NO --> cGMP --> PKG signal transduction pathway. |
| Databáze: | OpenAIRE |
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