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Article: Oxysterols Induce Cyclooxygenase-2 Expression in Cholangiocytes: Implications for Biliary Tract Carcinogenesis

TitleOxysterols Induce Cyclooxygenase-2 Expression in Cholangiocytes: Implications for Biliary Tract Carcinogenesis
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2004
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2004, v. 39 n. 3, p. 732-738 How to Cite?
AbstractCyclooxygenase-2 (COX-2), which is expressed by cholangiocytes in biliary tract disorders, has recently been implicated in biliary tract carcinogenesis. The mechanisms responsible for this COX-2 expression remain unclear. In human diseases, bile contains oxygenated derivatives of cholesterol (oxysterols) which possess diverse biological properties. Therefore, we determined if oxysterols modulate COX-2 expression. The effect of an oxysterol (22(R)-hydroxycholesterol, 22-HC) on COX-2 expression in KMBC cells, a human cholangiocarcinoma cell line, was examined. 22-HC enhanced COX-2 protein expression. This oxysterol activated p42/44 and p38 MAPK, but not JNK 1/2. A p42/44 MAPK inhibitor did not block COX-2 induction, while p38 MAPK inhibitor effectively attenuated COX-2 induction. Although COX-2 mRNA levels were increased by 22-HC, this increase was not transcriptionally regulated, as 22-OH did not increase activity in a COX-2 promoter gene assay. In contrast, COX-2 mRNA stability was augmented by 22-HC treatment, and this effect was reversed by a p38 MAPK inhibitor. In conclusion, the results demonstrate that the oxysterol 22-HC stabilizes COX-2 mRNA via a p38 MAPK-dependent mechanism. This enhanced COX-2 protein expression by oxysterols may participate in the genesis and progression of cholangiocarcinoma.
Persistent Identifierhttp://hdl.handle.net/10722/92469
ISSN
2023 Impact Factor: 12.9
2023 SCImago Journal Rankings: 5.011
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYoon, JHen_HK
dc.contributor.authorCanbay, AEen_HK
dc.contributor.authorWerneburg, NWen_HK
dc.contributor.authorLee, SPen_HK
dc.contributor.authorGores, GJen_HK
dc.date.accessioned2010-09-17T10:47:12Z-
dc.date.available2010-09-17T10:47:12Z-
dc.date.issued2004en_HK
dc.identifier.citationHepatology, 2004, v. 39 n. 3, p. 732-738en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92469-
dc.description.abstractCyclooxygenase-2 (COX-2), which is expressed by cholangiocytes in biliary tract disorders, has recently been implicated in biliary tract carcinogenesis. The mechanisms responsible for this COX-2 expression remain unclear. In human diseases, bile contains oxygenated derivatives of cholesterol (oxysterols) which possess diverse biological properties. Therefore, we determined if oxysterols modulate COX-2 expression. The effect of an oxysterol (22(R)-hydroxycholesterol, 22-HC) on COX-2 expression in KMBC cells, a human cholangiocarcinoma cell line, was examined. 22-HC enhanced COX-2 protein expression. This oxysterol activated p42/44 and p38 MAPK, but not JNK 1/2. A p42/44 MAPK inhibitor did not block COX-2 induction, while p38 MAPK inhibitor effectively attenuated COX-2 induction. Although COX-2 mRNA levels were increased by 22-HC, this increase was not transcriptionally regulated, as 22-OH did not increase activity in a COX-2 promoter gene assay. In contrast, COX-2 mRNA stability was augmented by 22-HC treatment, and this effect was reversed by a p38 MAPK inhibitor. In conclusion, the results demonstrate that the oxysterol 22-HC stabilizes COX-2 mRNA via a p38 MAPK-dependent mechanism. This enhanced COX-2 protein expression by oxysterols may participate in the genesis and progression of cholangiocarcinoma.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleOxysterols Induce Cyclooxygenase-2 Expression in Cholangiocytes: Implications for Biliary Tract Carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/hep.20125en_HK
dc.identifier.pmid14999691-
dc.identifier.scopuseid_2-s2.0-1542724860en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1542724860&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume39en_HK
dc.identifier.issue3en_HK
dc.identifier.spage732en_HK
dc.identifier.epage738en_HK
dc.identifier.isiWOS:000220427900019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYoon, JH=16246591600en_HK
dc.identifier.scopusauthoridCanbay, AE=6603790151en_HK
dc.identifier.scopusauthoridWerneburg, NW=6602569337en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK
dc.identifier.scopusauthoridGores, GJ=35397007900en_HK
dc.identifier.issnl0270-9139-

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