RRC ID 71713
著者 Bamba H, Ota S, Kato A, Kawamoto C, Fujiwara K.
タイトル Prostaglandins up-regulate vascular endothelial growth factor production through distinct pathways in differentiated U937 cells.
ジャーナル Biochem Biophys Res Commun
Abstract We previously reported that cyclooxygenase (COX)-2 was predominantly expressed in macrophages of human colonic adenomas (Int. J. Cancer 83, 470-475.). The role of prostaglandins (PGs) produced by COX-2-expressing macrophages in colon carcinogenesis is still unclear. Here we show that PGs up-regulate vascular endothelial growth factor (VEGF) production by activated macrophages through their specific receptors. mRNAs of both PGE-specific receptors and peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily of ligand-dependent transcription factors, were expressed in phorbol 12-myristate 13-acetate-differentiated U937, a human macrophage model (H-Mac). Prostaglandin E(1) (PGE(1)) and 15-deoxy-Delta(12,14)-PGJ(2) (a potent PPARgamma ligand, 15d-PGJ(2)) dramatically increased VEGF production. The combination of PGE(1) and 15d-PGJ(2) additively increased VEGF production. In addition, PGE(1) significantly increased cAMP formation, whereas 15d-PGJ(2) did not affect cAMP formation. The effect of the combination of PGE(1) and 15d-PGJ(2) on cAMP formation was similar to that of PGE(1) alone. Unexpectedly, 15d-PGJ(2) also drastically increased IL-1beta production, an indicator of macrophage activation, although PGE(1) only mildly increased it. Additional enhancement of IL-1beta production was observed in the combination of PGE(1) and 15d-PGJ(2). These results suggest that PGs dramatically increased VEGF production by activated macrophages through specific PGE receptor and PPARgamma-mediated processes and that PGs may thereby promote tumor growth through VEGF production.
巻・号 273(2)
ページ 485-91
公開日 2000-7-5
DOI 10.1006/bbrc.2000.2969
PII S0006-291X(00)92969-3
PMID 10873632
MeSH Alprostadil / pharmacology* Base Sequence Colonic Neoplasms / etiology Cyclic AMP / metabolism Cyclic AMP / pharmacology Cyclooxygenase 2 DNA Primers / genetics Endothelial Growth Factors / biosynthesis* Humans Interleukin-1 / biosynthesis Isoenzymes / metabolism Lymphokines / biosynthesis* Macrophage Activation Macrophages / drug effects Macrophages / metabolism Membrane Proteins Prostaglandin D2 / analogs & derivatives* Prostaglandin D2 / pharmacology Prostaglandin-Endoperoxide Synthases / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism Receptors, Prostaglandin E / genetics Receptors, Prostaglandin E / metabolism Transcription Factors / genetics Transcription Factors / metabolism U937 Cells Up-Regulation / drug effects Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
IF 2.985
リソース情報
ヒト・動物細胞 U-937 DE-4(RCB0435)