Asthma is one of the most chronic and morbid diseases affecting children worldwide. Cytokines are very important mediators of bronchial inflammation which is directly associated with asthma. Because of the intense and intricate interaction of cytokine networks, it is imperative that a comprehensive profile of cytokine gene expression be determined. Eosinophils are the principal cells involved in allergic inflammation. T cell cytokines IL-3, IL-5 and GM-CSF activate eosinophils which once activated can synthesize these cytokines themselves, thus creating chronic perpetual eosinophil activation with resultant destruction to the surrounding lung epithelia by release of toxic granules. Eosinophil cytokine receptors are a very significant components of the cytokine communication system and may regulate eosinophil recruitment. Therefore, a profile of the above cytokine receptor mRNA levels would provide a more comprehensive picture of the role of cytokines in bronchial inflammation. Eosinophils will be collected from blood samples of large atopic asthmatic families. The reverse transcriptase polymerase chain reaction will be used to detect mRNA in eosinophils for both cytokines and their receptors in atopic asthmatics, asthmatics, atopics, and nonatopic/nonasthmatic subgroups within families. Northern blot analysis will be performed on the PCR products. Additionally modulation of cytokine receptors by glucocorticoids and cromolyn (agents used in the treatment of asthma) will be evaluated Flow Cytometrically. Segregation analysis will be performed using cytokine, cytokine receptor mRNA levels and receptor density as phenotypes of bronchial inflammation. These gene products may be critical sites for therapeutic targeting in the war against asthma morbidity and mortality.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1996
Total Cost
Indirect Cost
Popa, Laurentiu S; Hewitt, Angela L; Ebner, Timothy J (2013) Purkinje cell simple spike discharge encodes error signals consistent with a forward internal model. Cerebellum 12:331-3
Fuller, T L; Canada, R G (1999) Enhancement of cisplatin cytotoxicity by terbium in cisplatin-resistant MDA/CH human breast cancer cells. Cancer Chemother Pharmacol 44:249-52
Canada, R G; Paltoo, D N (1998) Binding of terbium and cisplatin to C13* human ovarian cancer cells using time-resolved terbium luminescence. Biochim Biophys Acta 1448:85-98
Paltoo, D N; Canada, R G (1998) Effects of terbium on the cytotoxicity of cisplatin in FaDu human head and neck squamous cell carcinoma. Cancer Biochem Biophys 16:213-27
Ting, P; Cushenberry, P A; Friedman, T C et al. (1997) Enhanced brain opioid receptor activity precedes blood-brain barrier disruption. Acta Neurochir Suppl 70:250-3
Mack, K M; Canada, R G; Andrews, P A (1997) The effects of terbium on the cellular accumulation of cisplatin in MDA-MB-231 human breast tumor cells. Cancer Chemother Pharmacol 39:217-22
Dennis, G C; Dehkordi, O; Millis, R M et al. (1996) Monitoring of median nerve somatosensory evoked potentials during cervical spinal cord decompression. J Clin Neurophysiol 13:51-9
Canada, R G; Andrews, P A; Mack, K M et al. (1995) The effects of terbium on the accumulation of cisplatin in human ovarian cancer cells. Biochim Biophys Acta 1267:25-30
Ting, P; Xu, S; Krumins, S (1994) Endogenous opioid system activity following temporary focal cerebral ischemia. Acta Neurochir Suppl (Wien) 60:253-6
Canada, R G (1993) Calcium receptor binding of cisplatin and terbium in human breast tumor cells after hyperthermia. Radiat Res 133:170-5