Apoptosis signals in atopy and asthma measured with cDNA arrays

A variety of studies have stressed the importance of the control of inflamm atory cell longevity and the balance of pro-survival and pro-apoptotic sign alling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investiga te the systemic activation of apoptosis pathways using cDNA array technolog y in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-as thmatic (AN) and 14 healthy control subjects (C) were included in the study . Peripheral blood mononuclear cells were separated with gradient centrifug ation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expresse d genes and group differences assessed with the Mann-Whitney U-test. We fou nd a concerted up-regulation of several pro-survival cytokines and growth f actors in AN and AA. FAS and FASL were not differentially expressed, but FA ST kinase was over-expressed in AN and AA. The tumour necrosis factor pathw ay was activated in AN and AA with increased cytokine and receptor levels a nd increased TRAF2, an intracellular signalling product. There were indicat ions of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases sho wed a constant gene expression pattern in all groups. In conclusion, signif icant differences in the expression of apoptosis-related genes were found i n peripheral blood of atopic individuals with and without asthma. cDNA arra y technology proved to be useful and may be complementary to DNA-based stud ies in order to analyse interactive and multidimensional pathways as shown here for apoptosis.