Cigarette smoke stimulates cathepsin B activity in alveolar macrophages of rats.
ABSTRACT Cathepsin B activity was determined in alveolar macrophages and cell-free bronchoalveolar lavage fluid from Sprague-Dawley rats exposed only through the nose to fresh mainstream smoke from University of Kentucky high-tar, high-nicotine reference cigarettes, and in cells and fluid from room control and sham control animals. Increased levels of blood carboxyhemoglobin and pulmonary aryl hydrocarbon hydroxylase activity in smoke-exposed animals indicated effective exposure of animals to cigarette smoke. Cathepsin B activity was quantitated with alpha-N-benzyloxycarbonyl-leucine-leucine-arginine-2-naphthylamide as substrate. Specific activity (nanomoles of substrate cleaved per milligram of protein per hour) in alveolar macrophages was increased by 43% at both 4- and 10-week exposure points in animals exposed twice daily to 10 puffs of cigarette smoke. These data indicate that maximal stimulation of the enzyme occurs within 4 weeks of the initiation of smoke exposure. When the activity was expressed on a per-cell basis, cathepsin B activity was also increased in the smoke-exposed group at both exposure points. Activity in bronchoalveolar lavage fluid of smoke-exposed animals was increased by approximately 50% at 4 and 10 weeks, but the differences were not statistically significant. These findings demonstrate that cigarette smoke is a potent inducer of cathepsin B activity in alveolar macrophages of rats.
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ABSTRACT: Cigarette smoke, which contains several carcinogens known to initiate and promote tumorigenesis and metastasis, is the major cause of oral cancer. Lysosomal cathepsin proteases play important roles in tumor progression, invasion and metastasis. In the present work we investigated the effects of cigarette smoke condensate (CSC) on cathepsin (B, D and L) expression and protease-mediated invasiveness in human oral squamous cell carcinoma (OSCC) cells. Our results show that treatment of OSCC cells (686Tu and 101A) with CSC activated cathepsins B, D and L in a dose-dependent manner. Both expression and activity of these cathepsins were up-regulated in CSC-exposed versus non-exposed cells. Although cathepsin L had the lowest basal level, it had the highest induction in exposed cells compared to cathepsins B and D. Suppression of CSC-induced cathepsin B and L activities by specific chemical inhibitors decreased the invasion process, suggesting that these proteases are involved in the invasion process. Overall, our results indicate that CSC activates cathepsin B and L proteolytic activity and enhances invasiveness in OSCC cells, a response that may play a role in CSC-mediated tumor progression and metastasis dissemination.Toxicology Letters 04/2007; 170(2):134-45. DOI:10.1016/j.toxlet.2007.02.014 · 3.36 Impact Factor
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ABSTRACT: This review summarizes the current data on the effects of smoking and tobacco on the immune system and its potential impact on periodontal health. Smokers are 2.5-6 times more likely to develop periodontal disease than non-smokers, and there is evidence for a direct correlation between the number of cigarettes smoked and the risk of developing disease. Tobacco users also tend to exhibit increased severity of periodontal disease. Direct correlations between tobacco use and increased attachment loss and pocket depth and reduced bone crest height have been reported. Although the correlation between tobacco use and periodontal disease is quite strong, the role of tobacco in the pathogenesis of periodontal disease is uncertain. Recent studies indicate that one potential mechanism is that tobacco use exacerbates periodontal disease because it alters the immune response to periodontal pathogens. Indeed, smokers exhibit increased numbers of peripheral blood mononuclear phagocytes which appear to be functionally compromised. Inadequate phagocyte activity could reduce the clearance of pathogens from the oral cavity and thereby facilitate the development of periodontal disease. Tobacco-exposed B- and T-lymphocytes exhibit reduced proliferative capacities which could limit the production of protective immunoglobulins against oral pathogens. The risk factors for periodontal disease can be broadly classified as genetic, environmental, host-response factors, and host-related factors such as age. Tobacco, an environmental factor, undermines the host response and may facilitate the development and progression of periodontal disease. This review highlights the inter-relatedness of two of the risk factors associated with periodontal disease.Critical Reviews in Oral Biology & Medicine 02/1997; 8(4):437-60. DOI:10.1177/10454411970080040501
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ABSTRACT: Neutrophil elastase (NE) activity is increased in lung diseases such as alpha(1)-antitrypsin (A1AT) deficiency and pneumonia. It has recently been shown to induce expression of cathepsin B and matrix metalloprotease 2 (MMP-2) in vitro and in a mouse model. It is postulated that increased cathepsin B and MMP-2 in acute and chronic lung diseases result from high levels of extracellular NE and that expression of these proteases could be inhibited by A1AT augmentation therapy. Cathepsin and MMP activities were assessed in bronchoalveolar lavage (BAL) fluid from patients with A1AT deficiency, pneumonia and control subjects. Macrophages were exposed to BAL fluid rich in free NE from patients with pneumonia following pretreatment with A1AT. MMP-2, cathepsin B, secretory leucoprotease inhibitor (SLPI) and lactoferrin levels were determined in BAL fluid from A1AT-deficient patients before and after aerosolisation of A1AT. BAL fluid from both patients with pneumonia and those with A1AT deficiency containing free NE had increased cathepsin B and MMP-2 activities compared with BAL fluid from healthy volunteers. The addition of A1AT to BAL fluid from patients with pneumonia greatly reduced NE-induced cathepsin B and MMP-2 expression in macrophages in vitro. A1AT augmentation therapy to A1AT-deficient individuals also reduced cathepsin B and MMP-2 activity in BAL fluid in vivo. Furthermore, A1AT-deficient patients had higher levels of SLPI and lactoferrin after A1AT augmentation therapy. These findings suggest a novel role for A1AT inhibition of NE-induced upregulation of MMP and cathepsin expression both in vitro and in vivo.Thorax 08/2008; 63(7):621-6. DOI:10.1136/thx.2007.088559 · 8.56 Impact Factor