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Biomedical subjects

Heike Bantel

Publications and source records attributed to Heike Bantel.

6 recordsLinked to original sources
PubMed2006

Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection.

Only half of patients with chronic hepatitis C virus (HCV) infection and genotype-1 show a sustained antiviral response to the current antiviral therapy. The reason this treatment fails is unclear, and no reliable marker exists that predicts the treatment outcome. In the present study, we investigated the apoptotic activation of caspases in HCV patients undergoing antiviral therapy with regard to the treatment outcome. We determined caspase activation in sera from patients who were either responding or nonresponding to antiviral therapy by using two novel caspase assays, an immunological and a luminometric enzyme test. We found that compared with nonresponding individuals, responding patients showed significantly (P < .05) increased caspase activity, which was closely correlated with virus elimination (r = 0.81). The cutoff value of serum caspase activity was determined, which correctly predicted the treatment outcome with a sensitivity of 70% and a specificity of 82% (area under the curve 0.845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy.

Adult↗
PubMed2005

Caspase activation is involved in chronic periodontitis.

Periodontitis, a common infectious disease, is initiated by various gram-negative bacteria and characterized by the destruction of the periodontal tissue. Here, we investigated the role of caspases, intracellular proteases that are the key mediators of apoptosis. We show that activation of caspase-3 and caspase-7 is considerably enhanced in gingival tissue from patients with periodontitis. We also demonstrate in in vitro experiments that various periodontopathic bacteria exert a direct growth-suppressing effect and, moreover, can trigger a host-mediated cytotoxic activity involving the CD95 death receptor. Our data suggest that caspase activation is a prominent feature in periodontitis-associated tissue injury.

Adult↗
PubMed2005

The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum.

Hepatic steatosis is a frequent histological alteration in chronic hepatitis C virus (HCV) infection that sensitizes the liver to cell injury, inflammation, and fibrosis via unclear mechanisms. Although apoptosis has been implicated in various liver diseases, its importance in HCV-associated steatosis is largely unknown. In this study, we investigated the role of caspases, the key regulators of apoptosis, and employed two novel caspase assays, an immunological and a luminometric enzyme test, to detect hepatic caspase activation in sera from HCV patients with different grades of steatosis. Our data show that increased caspase activation can be found not only in liver biopsies, but also in sera from HCV patients with liver steatosis. Patients with steatosis exhibited significantly higher serum levels of caspase activity compared with normal healthy individuals. Moreover, the extent of steatosis closely correlated with serum caspase activity, whereas in particular in cases of low or moderate steatosis, no correlation was found with aminotransferase levels. In conclusion, apoptotic caspase activation is considerably elevated in HCV-associated steatosis. More importantly, our data imply that measurement of caspase activation might be a sensitive serum biomarker to detect liver steatosis in patients with chronic HCV infection and other liver diseases.

Adult↗
PubMed2004

Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury.

Chronic hepatitis C virus (HCV) infection is characterized by inflammatory liver damage and is associated with a high risk of development of cirrhosis and hepatocellular carcinoma. Although histological examination of liver biopsies is currently the gold standard for the detection of early liver damage, there is a strong need for better noninvasive methods. We recently demonstrated that the proapoptotic activation of caspases is considerably enhanced in histological sections from HCV-infected liver tissue, suggesting an important role of apoptosis in liver damage. Here, we investigated whether caspase activation is detectable also in sera from patients with chronic HCV infection. Using a novel enzyme-linked immunosorbent assay that selectively recognizes a proteolytic neoepitope of the caspase substrate cytokeratin-18, we demonstrate that caspase activity is markedly increased in the sera of HCV patients. Interestingly, while 27% of patients with chronic HCV infection showed normal aminotransferase levels despite inflammatory and fibrotic liver damage, more than 50% of those patients exhibited already elevated serum caspase activity. Moreover, 30% of patients with normal aminotransferase but elevated caspase activity revealed higher stages of fibrosis. In conclusion, compared with conventional surrogate markers such as aminotransferases, detection of caspase activity in serum might be a more sensitive method of detecting early liver injury. Thus, measurement of caspase activity might provide a novel diagnostic tool, especially for patients with normal aminotransferases but otherwise undiagnosed histologically active hepatitis and progressive fibrosis.

Adult↗
PubMed2002

Critical role of NF-kappaB and stress-activated protein kinases in steroid unresponsiveness.

Glucocorticoid resistance is a serious clinical problem in chronic inflammatory diseases, because many patients with rheumatoid arthritis, asthma, or Crohn's disease fail to respond to steroid treatment. The molecular mechanisms underlying this unresponsiveness, however, are completely unknown. The effects of steroids are largely mediated by the interference of the glucocorticoid receptor (GR) with proinflammatory transcription factors. In the present study, we therefore investigated the activation of the transcription factors nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and the upstream kinases p38 and c-Jun N-terminal kinase (JNK) in steroid-sensitive and steroid-resistant patients with Crohn's disease. We demonstrated that steroid-sensitive and steroid-resistant patients reveal a remarkably different cellular activation pattern of these proinflammatory mediators. In steroid-sensitive patients, activation of NF-kappaB, AP-1, p38, and JNK was mainly found in lamina propria macrophages. In contrast, steroid-resistant patients revealed activation of all these mediators mostly in epithelial cells. The functional interference of the proinflammatory mediators with the glucocorticoid response was supported by reporter gene assays. Expression of NF-kappaB and, interestingly, also JNK1 and p38 inhibited the activity of the GR. Thus, our results suggest that steroid resistance is associated with increased epithelial activation of stress-activated protein kinases and NF-kappaB, which might inhibit the anti-inflammatory action of a limited number of GRs.

Caco-2 Cells↗