The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice.

Ahmada, Sheikh Fayaz and Zoheir, Khairy M.A. and Ansari, Mushtaq Ahmad and Korashya, Hesham M. and Bakheet, Saleh A. and Ashour, Abdelkader Elbadawy Abbas and Al-Shabanaha, Othman A. and Al-harbi, Mohammed M. and Attiaa, Sabry M. (2015) The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. Molecular Immunology, 63 (2). pp. 394-405. ISSN 0161-5890

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Abstract

Increasing indication is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. The aim of the present study was to determine the potential anti-inflammatory effects of PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ) to explore the role of PARP-1 inhibitor in a mouse model of carrageenan-induced lung inflammation. A single dose of 5-AIQ (1.5mg/kg) was administered intraperitoneally (i.p.) 1h before λ-carrageenan (Cg) administration. We assessed the effects of 5-AIQ treatment on CD25(+), GITR(+), CD25(+)GITR(+), IL-17(+) and Foxp3(+) cells which were investigated using flowcytometry in pleural exudates and heparinized blood. We also evaluated mRNA expressions of IL-6, TNF-α, IL-1β, IL-10, CD11a, l-selectin (CD62L), ICAM-1, MCP-1, iNOS and COX-2 in the lung tissue. We further examined the effects of 5-AIQ on the key mediators of inflammation, namely COX-2, STAT-3, NF-kB p65, PARP-1, IkB-α and IL-4 protein expression in the lung tissue using western blotting. The results illustrated that the numbers of T cell subsets, IL-17(+) cytokine levels were markedly increased and Foxp3(+) production decreased in the Cg group. Furthermore, Cg-induced up-regulation of adhesion molecules, pro-inflammatory mediators and chemokine expressions. Western blot analysis revealed an increased protein expressions of COX-2, STAT-3 NF-kB p65 and PARP-1 and decreased IkB-α and IL-4 in the Cg group. PARP-1 inhibitor via 5-AIQ treatment reverses the action significantly of all the previously mentioned effects. Moreover, histological examinations revealed anti-inflammatory effects of 5-AIQ, whereas Cg-group aggravated Cg-induced inflammation. Present findings demonstrate the potent anti-inflammatory action of the PARP-1 inhibitor in acute lung injury induced by carrageenan.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Carrageenan; PARP-1 inhibitor; Inflammatory mediators; Pleural exudate; Lung tissue
Subjects:	R Medicine > RB Pathology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical
Depositing User:	Dr. Abdelkader Ashour
Date Deposited:	06 Jan 2019 15:43
Last Modified:	06 Jan 2019 15:43
URI:	http://irep.iium.edu.my/id/eprint/66953

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