ß-Catenin triggers nuclear factor ?B-dependent up-regulation of hepatocyte inducible nitric oxide synthase

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

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Interleukin-1β, inducible nitric oxide synthase, and nuclear factor-κB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-γ injection

Journal of Neuroscience Research ◽

10.1002/(sici)1097-4547(19990801)57:3<388::aid-jnr11>3.0.co;2-2 ◽

1999 ◽

Vol 57 (3) ◽

pp. 388-398 ◽

Cited By ~ 60

Author(s):

Maike Hartlage-Rübsamen ◽

Rainer Lemke ◽

Reinhard Schliebs

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Nuclear Factor Κb ◽

Interferon Γ ◽

Interleukin 1Β ◽

Nuclear Factor ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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Isolation and characterization of cytotoxic and anti-inflammatory constituents from Scoparia dulcis L

Journal of Chemical Research ◽

10.1177/1747519819901100 ◽

2020 ◽

Vol 44 (7-8) ◽

pp. 381-387

Author(s):

Mohammad Nur-e-Alam ◽

Sarfaraz Ahmed ◽

Muhammad Yousaf ◽

Shabana I Khan ◽

Ramzi A Mothana ◽

...

Keyword(s):

Nitric Oxide ◽

Acetic Acid ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Scoparia Dulcis ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.

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