Suppression of inducible nitric oxide synthase and tumor necrosis factor-alpha expression by 4-nonylphenol in macrophages.
4-Nonylphenol (NP) is reported to have estrogenic activity; however, its influence on cytokine production or immune system function remains unclear. In this study we investigated the effects of NP on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse macrophages. NP alone did not affect NO or TNF-alpha production. In contrast, NP inhibited lipopolysaccharide (LPS)-induced NO and TNF-alpha production, and the levels of iNOS and TNF-alpha mRNA in a dose-dependent manner. Treatment with ICI 182.780, an estrogen-receptor antagonist, inhibited the suppressive effects of NP. NF-kappaB sites have been identified in the promoter of the iNOS and TNF-alpha genes. Transient expression and electrophoretic mobility shift assays with NF-kappaB binding sites revealed that NP reduced the levels of the LPS-induced NF-kappaB transcription factor complex. These results demonstrate that NP may affect the regulation of the immune system function by reducing NO and TNF-alpha production via the inhibition of NF-kappaB transactivation mediated through the estradiol receptor.
You
Ho Jin
HJ
Department of Pharmacology, School of Medicine, 375 Seosuk-dong, Kwangju 501-759, South Korea.
Choi
Chul Yung
CY
Jeon
Young Jin
YJ
Chung
Young Chul
YC
Kang
Shin Keon
SK
Hahm
Kyung-Soo
KS
Jeong
Hye Gwang
HG
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D000077267:Fulvestrant; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011959:Receptors, Estradiol / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D008070:Lipopolysaccharides; D010636:Phenols; D012333:RNA, Messenger; D011959:Receptors, Estradiol; D014409:Tumor Necrosis Factor-alpha; D000077267:Fulvestrant; D004958:Estradiol; D008156:Luciferases; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001616:beta-Galactosidase; C041594:4-nonylphenol