Interleukin-1α Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2: IMPLICATIONS FOR ALLOGRAFT REJECTION*

Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.     

Application of Rice-Straw Biochar and Microorganisms in Nonylphenol Remediation: Adsorption-Biodegradation Coupling Relationship and Mechanism

Biochar adsorption presents a potential remediation method for the control of hydrophobic organic compounds (HOCs) pollution in the environment. It has been found that HOCs bound on biochar become less bioavailable, so speculations have been proposed that HOCs will persist for longer half-life periods in biochar-amended soil/sediment. To investigate how biochar application affects coupled adsorption-biodegradation, nonylphenol was selected as the target contaminant, and biochar derived from rice straw was applied as the adsorbent. The results showed that there was an optimal dosage of biochar in the presence of both adsorption and biodegradation for a given nonylphenol concentration, thus allowing the transformation of nonylphenol to be optimized. Approximately 47.6% of the nonylphenol was biodegraded in two days when 0.005 g biochar was added to 50 mg/L of nonylphenol, which was 125% higher than the relative quantity biodegraded without biochar, though the resistant desorption component of nonylphenol reached 87.1%. All adsorptive forms of nonylphenol (f _rap, f _slow, f _r) decreased gradually during the biodegradation experiment, and the resistant desorption fraction of nonylphenol (f _r) on biochar could also be biodegraded. It was concluded that an appropriate amount of biochar could stimulate biodegradation, not only illustrating that the dosage of biochar had an enormous influence on the half-life periods of HOCs but also alleviating concerns that enhanced HOCs binding by biochar may cause secondary pollution in biochar-modified environment.     

Effects of estrogen deprivation on human benign prostatic hyperplasia

Sex steroids are thought to play an essential role in the pathogenesis of human benign prostatic hyperplasia (BPH). Since recent studies in animal models and in men have shown that estrogens might be causally linked to the onset and maintenance of BPH, we examined the effect of 1-methyl-androsta-1,4-diene-3,17-dione (Atamestane), a newly developed aromatase inhibitor, in men with BPH. In an open multicenter study 49 men (mean age 70.1 years, range 55 to 84) with obstructive BPH were treated with atamestane (3 × 200 mg/day) for 3 months. Of the 49 patients 44 completed the treatment period; the other patients discontinued the study for reasons unrelated to treatment. With treatment BPH-related symptoms such as daytime voiding frequency, nycturia, peak flow and residual urine improved considerably; however, these parameters did not reach statistical significance. The mean prostatic volume decreased significantly from 74.2 ± 31.7 to 64.0 ± 31 ml (mean ± SD). Serum estrogen levels decreased markedly during treatment. In addition intraprostatic estrogen concentration decreased with treatment as compared to estrogen levels in hyperplastic prostates from untreated patients. The following conclusions can be drawn from this study: first, estrogens appear to have an important supportive role in established BPH, and second, estrogen deprivation improved BPH-related symptoms and reduced significantly prostatic volume.     

Near ultraviolet light inactivation of dihydroxyacid dehydratase in Escherichia coli

The effects of near ultraviolet (NUV) light on a NUV chromophore-containing oxidant-sensitive enzyme, dihydroxyacid dehydratase (DHAD), were measured in seven strains of Escherichia coli. The strains differed in production of the oxidant-defense enzymes, superoxide dismutases (Fe-SOD and Mn-SOD), and catalases HPI and HPII. With the stress of aerobic growth but without NUV exposure, the strains lacking either Fe or Mn SOD or both SODs had 57%, 25%, and 12%, respectively, of the DHAD-specific activity of the parent (K12) strain. Under the same conditions, the catalase strains that were wild type, overproducing, and deficient had comparable DHAD-specific activities. When aerobic cultures were exposed for 30 min to NUV with a fluence of 216 J/m²/s at 310–400 nm, the percentage decreases in DHAD-specific activities were similar (ranging from 75% to 89%) in strains with none, either, or both SODs missing, and in the catalase-overproducing strain. However, the decreases were only 58% and 52% in the strain with catalase missing and in its parent, respectively. The NUV-induced loss of DHAD enzyme activity was not accompanied by any detectable loss of the DHAD protein as measured by polyclonal antibody to DHAD.     

Knowledge-based simulation of DNA metabolism: prediction of enzyme action

We have developed a knowledge-based simulation of DNA metabolismthat accurately predicts the actions of enzymes on DNA undera large number of environmental conditions. Previous simulationsof enzyme systems rely predominantly on mathematical models.We use a frame-based representation to model enzymes, substratesand conditions. Interactions between these objects are expressedusing production rules and an underlying truth maintenance system.The system performs rapid inference and can explain its reasoning.A graphical interface provides access to all elements of thesimulation, including object representations and explanationgraphs. Predicting enzyme action is the first step in the developmentof a large knowledge base to envision the metabolic pathwaysof DNA replication and repair. Received on February 1, 1990; accepted on October 2, 1990