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The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice.
Mol Immunol. 2015 Feb; 63(2):394-405.MI

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: s_fayazahmad@yahoo.com.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Cell Biology, National Research Centre, Cairo, Egypt.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25304310

Citation

Ahmad, Sheikh Fayaz, et al. "The Role of poly(ADP-ribose) Polymerase-1 Inhibitor in Carrageenan-induced Lung Inflammation in Mice." Molecular Immunology, vol. 63, no. 2, 2015, pp. 394-405.
Ahmad SF, Zoheir KM, Ansari MA, et al. The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. Mol Immunol. 2015;63(2):394-405.
Ahmad, S. F., Zoheir, K. M., Ansari, M. A., Korashy, H. M., Bakheet, S. A., Ashour, A. E., Al-Shabanah, O. A., Al-harbi, M. M., & Attia, S. M. (2015). The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. Molecular Immunology, 63(2), 394-405. https://doi.org/10.1016/j.molimm.2014.09.009
Ahmad SF, et al. The Role of poly(ADP-ribose) Polymerase-1 Inhibitor in Carrageenan-induced Lung Inflammation in Mice. Mol Immunol. 2015;63(2):394-405. PubMed PMID: 25304310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. AU - Ahmad,Sheikh Fayaz, AU - Zoheir,Khairy M A, AU - Ansari,Mushtaq Ahmad, AU - Korashy,Hesham M, AU - Bakheet,Saleh A, AU - Ashour,Abdelkader E, AU - Al-Shabanah,Othman A, AU - Al-harbi,Mohammed M, AU - Attia,Sabry M, Y1 - 2014/10/07/ PY - 2014/05/28/received PY - 2014/09/07/revised PY - 2014/09/17/accepted PY - 2014/10/12/entrez PY - 2014/10/12/pubmed PY - 2015/3/7/medline KW - Carrageenan KW - Inflammatory mediators KW - Lung tissue KW - PARP-1 inhibitor KW - Pleural exudate SP - 394 EP - 405 JF - Molecular immunology JO - Mol Immunol VL - 63 IS - 2 N2 - 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. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/25304310/The_role_of_poly_ADP_ribose__polymerase_1_inhibitor_in_carrageenan_induced_lung_inflammation_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(14)00254-5 DB - PRIME DP - Unbound Medicine ER -