PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice.
Bottom Line: Our results show that PARP is activated in PBMCs and lung tissues of asthmatics.These effects were linked to a marked reduction in T helper 2 (Th2) cytokine production without a prominent effect on interferon (IFN)-γ or interleukin (IL)-10.In CD3/CD28-stimulated human CD4 (+)T-cells, olaparib treatment reduced Th2 cytokine production potentially by modulating GATA binding protein-3 (gata-3)/IL-4 expression while moderately affecting T-cell proliferation.
Affiliation: The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A. Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt.Show MeSH
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Mentions: We next examined whether PARP inhibition pharmacologically by olaparib or genetically by gene knockout blocks asthma-like manifestation upon intraneural (i.n.) administration of HDM. Figure 2 (A) shows that a single administration of olaparib at the end of the HDM exposure protocol was highly effective in decreasing recruitment of eosinophils and macrophages as well as overall cellularity in the lungs. However, the increase in the number of lymphocytes was not affected. A remarkable protection was achieved upon two additional administrations of the drug including a reduction in the number of lymphocytes. Similar results were observed in HDM-exposed PARP-1−/− mice, which provide evidence for the specificity of such protective effects. Interestingly, repeated administration of olaparib provided significantly better reduction in recruitment of the total number of inflammatory cells, eosinophils and macrophages, than that provided by PARP-1 gene deletion.
Affiliation: The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A. Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt.