{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:04:44Z","timestamp":1790928284494,"version":"4.1.0"},"reference-count":32,"publisher":"Portland Press Ltd.","issue":"11","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:p>Our laboratory established a role for poly(ADP-ribose)polymerase (PARP) in asthma. To increase the clinical significance of our studies, it is imperative to demonstrate that PARP is actually activated in human asthma, to examine whether a PARP inhibitor approved for human testing such as olaparib blocks already-established chronic asthma traits in response to house dust mite (HDM), a true human allergen, in mice and to examine whether the drug modulates human cluster of differentiation type 4 (CD4+) T-cell function. To conduct the study, human lung specimens and peripheral blood mononuclear cells (PBMCs) and a HDM-based mouse asthma model were used. Our results show that PARP is activated in PBMCs and lung tissues of asthmatics. PARP inhibition by olaparib or gene knockout blocked established asthma-like traits in mice chronically exposed to HDM including airway eosinophilia and hyper-responsiveness. These effects were linked to a marked reduction in T helper 2 (Th2) cytokine production without a prominent effect on interferon (IFN)-\u03b3 or interleukin (IL)-10. PARP inhibition prevented HDM-induced increase in overall cellularity, weight and CD4+ T-cell population in spleens of treated mice whereas it increased the T-regulatory cell population. 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. PARP inhibition inconsistently increased IL-17\u00a0in HDM-exposed mice and CD3\/CD28-stimulated CD4+ T cells without a concomitant increase in factors that can be influenced by IL-17. In the present study, we provide evidence for the first time that PARP-1 is activated in human asthma and that its inhibition is effective in blocking established asthma in mice.<\/jats:p>","DOI":"10.1042\/cs20150122","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T01:39:56Z","timestamp":1437701996000},"page":"951-962","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice"],"prefix":"10.1042","volume":"129","author":[{"given":"Mohamed\u00a0A.","family":"Ghonim","sequence":"first","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."},{"name":"Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kusma","family":"Pyakurel","sequence":"additional","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salome\u00a0V.","family":"Ibba","sequence":"additional","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Wang","sequence":"additional","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."},{"name":"Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir\u00a0A.","family":"Al-Khami","sequence":"additional","affiliation":[{"name":"The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A."},{"name":"Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew\u00a0R.","family":"Lammi","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Section, School of Medicine, Louisiana State University; 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