Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crystalline silica stimulates macrophages in vitro to release interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) and induces apoptosis of macrophages. Because the fibrogenic potential of a particulate paralleled its ability to induce apoptosis in macrophages, we investigated the underlying mechanisms by which IL-1beta and NO mediate apoptosis and inflammation in murine silicosis. First, we demonstrated that silica induced NO production and apoptosis in vitro using the IC-21 macrophage cell line. Both NO release and apoptosis could be inhibited by neutralizing anti-IL-1beta antibody or the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME), demonstrating the requirement for IL-1beta-mediated NO release in silica-induced apoptosis. We exposed IL-1beta knockout (IL-1beta(-/-)) mice, inducible NOS knockout (iNOS(-/-)) mice, and wild-type mice to 250 mg/m(3) silica for 5 h/d for 10 d using an inhalation chamber. Exposure of wild-type mice to silica resulted in lung inflammation, apoptosis, and significantly larger and more numerous silicotic lesions than in IL-1beta(-/-) mice over a 12-wk course. We also exposed iNOS(-/-) mice via inhalation in the same protocol and compared with wild-type mice and demonstrated that iNOS(-/-) mice had significantly reduced apoptosis and inflammation. These results demonstrated an association between apoptosis and inflammation in murine silicosis and support a potential role for IL-1beta-dependent NO-mediated apoptosis in the evolution of silicosis.
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PMID:Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. 1185 Mar 47

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid purified and identified an active ingredient in a Chinese medicinal herb, radix stephanae tetrandrae, has been used traditionally for the treatment of congestive circulatory disorder and inflammatory diseases. TET, together with a few of its structural analogues, has long been demonstrated to have antihypertensive action in clinical as well as animal studies. Presumably, the primary anti-hypertensive action of TET is due to its vasodilatory properties. TET prevents or inhibits vascular contraction induced by membrane depolarization with KCl or alpha-adrenoceptor activation with phenylephrine (PE). TET (30 micromol/L) also inhibits the release of endothelium-derived nitric oxide (NO) as well as NO production by inducible NO synthase. TET apparently inhibits multiple Ca2+ entry pathways as demonstrated in cell types lacking the L-type Ca2+ channels. In cardiac muscle cells, TET inhibits both L- and T-type Ca2+ channels. In addition to its actions on cardiovascular tissues, TET may also exert its anti-hypertensive action via a Ca2+-dependent manner on other tissues intimately involved in the modulation of blood pressure control, such as adrenal glands. In adrenal glomerulosa cells, KCl- or angiotensin II-induced aldosterone synthesis is highly dependent on extracellular Ca2+. Steroidogenesis and Ca2+-influx in bovine adrenal glomerulosa cells have been shown to be potently inhibited by TET. In bovine adrenal chromaffin cells, TET inhibits Ca2+ currents via L- and N-type channels as well as other unidentified channels with IC50 of 10 micromol/L. Other than the Ca2+ antagonistic effects, TET also interacts with the alpha-adrenergic receptors and muscarinic receptors based on functional as well as radioligand binding studies. Apart from its functional effects, TET and related compounds also exert effects on tissue structures, such as remodelling of hypertrophied heart and inhibition of angiogenesis, probably by causing apoptotic responses. TET is also known for its anti-inflammatory and anti-fibrogenic actions, which make TET and related compound potentially useful in the treatment of lung silicosis, liver cirrhosis, and rheumatoid arthritis.
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PMID:Tetrandrine and related bis-benzylisoquinoline alkaloids from medicinal herbs: cardiovascular effects and mechanisms of action. 1246 42