The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice.
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English English |
| Published: |
Elsevier
2015
|
| Subjects: | |
| Online Access: | http://irep.iium.edu.my/66953/ http://irep.iium.edu.my/66953/1/The%20role%20of%20poly%28ADP-ribose%29%20polymerase-1%20inhibitor%20in%20carrageenan-induced%20lung%20inflammation%20in%20mice..pdf http://irep.iium.edu.my/66953/7/66953_Scopus%20-%20Document%20details.pdf |
| _version_ | 1848786671536963584 |
|---|---|
| author | Ahmada, Sheikh Fayaz Zoheir, Khairy M.A. Ansari, Mushtaq Ahmad Korashya, Hesham M. Bakheet, Saleh A. Ashour, Abdelkader Elbadawy Abbas Al-Shabanaha, Othman A. Al-harbi, Mohammed M. Attiaa, Sabry M. |
| author_facet | Ahmada, Sheikh Fayaz Zoheir, Khairy M.A. Ansari, Mushtaq Ahmad Korashya, Hesham M. Bakheet, Saleh A. Ashour, Abdelkader Elbadawy Abbas Al-Shabanaha, Othman A. Al-harbi, Mohammed M. Attiaa, Sabry M. |
| author_sort | Ahmada, Sheikh Fayaz |
| building | IIUM Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T17:12:45Z |
| format | Article |
| id | iium-66953 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T17:12:45Z |
| publishDate | 2015 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | iium-669532019-01-06T07:43:46Z http://irep.iium.edu.my/66953/ The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. Ahmada, Sheikh Fayaz Zoheir, Khairy M.A. Ansari, Mushtaq Ahmad Korashya, Hesham M. Bakheet, Saleh A. Ashour, Abdelkader Elbadawy Abbas Al-Shabanaha, Othman A. Al-harbi, Mohammed M. Attiaa, Sabry M. RB Pathology 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. Elsevier 2015-02-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/66953/1/The%20role%20of%20poly%28ADP-ribose%29%20polymerase-1%20inhibitor%20in%20carrageenan-induced%20lung%20inflammation%20in%20mice..pdf application/pdf en http://irep.iium.edu.my/66953/7/66953_Scopus%20-%20Document%20details.pdf 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 https://www.journals.elsevier.com/molecular-immunology https://doi.org/10.1016/j.molimm.2014.09.009 |
| spellingShingle | RB Pathology Ahmada, Sheikh Fayaz Zoheir, Khairy M.A. Ansari, Mushtaq Ahmad Korashya, Hesham M. Bakheet, Saleh A. Ashour, Abdelkader Elbadawy Abbas Al-Shabanaha, Othman A. Al-harbi, Mohammed M. Attiaa, Sabry M. The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title | The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title_full | The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title_fullStr | The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title_full_unstemmed | The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title_short | The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| title_sort | role of poly(adp-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. |
| topic | RB Pathology |
| url | http://irep.iium.edu.my/66953/ http://irep.iium.edu.my/66953/ http://irep.iium.edu.my/66953/ http://irep.iium.edu.my/66953/1/The%20role%20of%20poly%28ADP-ribose%29%20polymerase-1%20inhibitor%20in%20carrageenan-induced%20lung%20inflammation%20in%20mice..pdf http://irep.iium.edu.my/66953/7/66953_Scopus%20-%20Document%20details.pdf |