A molecular cascade showing nitric oxide-heme oxygenase-1-vascular endothelial growth factor-interleukin-8 sequence in human endothelial cells.
Heme oxygenase (HO)-1 has been shown to be an important biological target of nitric oxide (NO). NO can induce HO-1 expression and IL-8 production, particularly, in endothelial cells. Interestingly, HO-1 tends to induce the production of vascular endothelial growth factor (VEGF) that is involved in endothelial IL-8 syntheses. Whether HO-1 expression by NO may provide a link with IL-8 or VEGF synthesis was investigated in human umbilical vein endothelial cells (HUVECs). The NO donor S-nitroso-N-acetyl-penicillamine (SNAP) dose-dependently increased IL-8 and VEGF productions and HO-1 expression in HUVECs. Transfection with either HO-1 small interfering RNA or HO-1 antisense oligodeoxynucleotide abrogated the ability of SNAP to induce HO-1 expression and IL-8 and VEGF productions. Both pharmacological induction and gene transfer of HO-1 directly induced IL-8 and VEGF productions. Anti-VEGF neutralizing antibody blocked SNAP-mediated IL-8 production and VEGF itself induced IL-8 production, whereas anti-IL-8 neutralizing antibody had no effect on VEGF production in SNAP-treated HUVECs. Neither anti-VEGF nor anti-IL-8 antibodies influenced SNAP-induced HO-1 expression. Moreover, neither VEGF nor IL-8 showed an additive effect on SNAP-induced HO-1 expression. HO-1 transfection had no significant effect on productions of other CXC chemokines, such as growth-related oncogen-alpha and epithelial neutrophil activation peptide-78. Taken together, these results provide a molecular cascade showing NO-HO-1-VEGF-IL-8 sequence in human endothelial cells.
Pae
Hyun-Ock
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Shinyoung-Dong, Iksan-Shi, Chonbug 570-749, Republic of Korea.
Oh
Gi-Su
GS
Choi
Byung-Min
BM
Kim
Young-Myeong
YM
Chung
Hun-Taeg
HT
D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D016209:Interleukin-8; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010396:Penicillamine