The Histone-AcétylTransférase on a war footing against asthma

Two studies by the University of Nottingham on the causes and treatment of asthma and Chronic Obstructives Pulmonary disease (COPD) could lead to the development of drugs combating these debilitating diseases.

The Department of Respiratory Medicine at the University was granted subsidies of £ 1.24 million to finance research on respiratory diseases. The Wellcome Trust has awarded to Professor Alan Knox and Dr Pang Linhua £ 700000 to study the transcriptional control of gene expression of inflammatory asthma - thus allowing the team to investigate the role of mediators inflammatory in the way asthmatics react to allergens. A second grant of £ 540000 MRC paid to Professor Knox and his colleagues, Professor Peter Fischer and Professor David Heery, the study will inhibitors of the histone acetyltransferase-in asthma and COPD. This study will examine a bank of plant extracts from the University of Strathclyde to try to find compounds that can fight the process Intercellular causing the symptoms of asthma and COPD - airway inflammation that causes coughing, " shortness of breath and chest infections increased.

Even if they are different diseases, asthma and COPD affect the human body in the same way. For asthma, allergens irritate the lungs; for COPD, cigarette smoke is the cause. This irritation inflames the airways of patients whose muscles are closing, creating an effect of narrowing.

Research conducted at the University over the past 15 years have led to the muscle layer airway is more complex than thought. While it produces spasms in asthma and COPD, the muscle layer produces a wide variety of mediators and cytokines - proteins which are used as chemical alarms after coming into contact with allergens or cigarette smoke. Among asthmatics and those who suffer from COPD, these proteins are produced by stimulation of muscle cell walls airways of the lungs, that release of intracellular signaling proteins called 'factors trabscription' which changes the DNA of the cell and activate mRNA. These are the 'transcription factors' that activate inflammation by releasing mediators and cytokines.

The activation status of these transcription factors is defined by the balance between two competing groups of enzymes-called histone acetyltransferase (HAT), and histone deacetylases (HDAC). Among asthmatics and those who suffer from COPD, the balance is altered - and the HAT activated and its HDAC removed, triggering inflammation. Researchers at the University believe that if the balance can be restored by disabling the HAT, mediators and cytokines also will be deactivated and inflammation eased.

Through exploration of the plant extracts may reduce the activation of HAT in the airway cells, researchers can isolate compounds used to suppress inflammation in respiratory diseases. If we were able to synthesize a drug from these compounds, respiratory disorders would be revolutionized. The potential also exists to treat other inflammatory diseases such as rheumatoid arthritis and Crohn's disease.

Professor Alan Knox, the Department of Respiratory Medicine at the University, said: "The majority of people with asthma have access to anti-inflammatory treatment good enough that allow them to maintain control of their disease. But nearly 20% of them do not respond adequately to existing treatments. And in terms of COPD, the anti-inflammatory drugs are not very effective.

"By retracing the process trigger inflammation and then identifying compounds that activate or inhibit these enzymes essential, we can launch the development of a drug that could produce an enormous effect on the lives of those who suffer from respiratory diseases and other inflammatory diseases. "