Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37
Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE2 in human gingival fibroblasts (HGFs). We, therefore,...
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th-cmuir.6653943832-40192014-08-30T02:35:35Z Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 Chotjumlong P. Bolscher J.G. Nazmi K. Reutrakul V. Supanchart C. Buranaphatthana W. Krisanaprakornkit S. Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE2 in human gingival fibroblasts (HGFs). We, therefore, aimed to examine the inducible effects of LL-37, the only cathelicidin expressed in humans, on COX-2 expression and PGE2 synthesis in HGFs and to elucidate the relevant signaling pathways. The COX-2 expression was upregulated by LL-37 in dose- and time-dependent manners. Accordingly, the synthesis of PGE2 in cell-free culture supernatants was raised by LL-37 (p < 0.01) and blocked by NS-398, a specific COX-2 inhibitor (p < 0.01). P2X inhibitors and a neutralizing antibody against P2X7 purinergic receptor significantly abrogated COX-2 induction and PGE2 production by LL-37 (p < 0.01). LL-37 upregulated COX-2 expression and PGE2 synthesis via activation of extracellular signal-regulated kinase (ERK) and p46 c-Jun N-terminal kinase (JNK), while interleukin-1β did so via nuclear factor-κB and all three mitogen-activated protein kinases. In summary, LL-37 can control arachidonic acid metabolism by induction of COX-2 expression and PGE2 synthesis via the P2X7 receptor, ERK, and p46 JNK. The pro-inflammatory effects of LL-37 may be essential for initiating oral mucosal inflammation in periodontal disease. Copyright © 2012 S. Karger AG, Basel. 2014-08-30T02:35:35Z 2014-08-30T02:35:35Z 2013 Article 1662811X 10.1159/000342928 23095809 http://www.scopus.com/inward/record.url?eid=2-s2.0-84872276132&partnerID=40&md5=ea2e6c670e2a54ef354c160f0b18cd68 http://cmuir.cmu.ac.th/handle/6653943832/4019 English |
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Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE2 in human gingival fibroblasts (HGFs). We, therefore, aimed to examine the inducible effects of LL-37, the only cathelicidin expressed in humans, on COX-2 expression and PGE2 synthesis in HGFs and to elucidate the relevant signaling pathways. The COX-2 expression was upregulated by LL-37 in dose- and time-dependent manners. Accordingly, the synthesis of PGE2 in cell-free culture supernatants was raised by LL-37 (p < 0.01) and blocked by NS-398, a specific COX-2 inhibitor (p < 0.01). P2X inhibitors and a neutralizing antibody against P2X7 purinergic receptor significantly abrogated COX-2 induction and PGE2 production by LL-37 (p < 0.01). LL-37 upregulated COX-2 expression and PGE2 synthesis via activation of extracellular signal-regulated kinase (ERK) and p46 c-Jun N-terminal kinase (JNK), while interleukin-1β did so via nuclear factor-κB and all three mitogen-activated protein kinases. In summary, LL-37 can control arachidonic acid metabolism by induction of COX-2 expression and PGE2 synthesis via the P2X7 receptor, ERK, and p46 JNK. The pro-inflammatory effects of LL-37 may be essential for initiating oral mucosal inflammation in periodontal disease. Copyright © 2012 S. Karger AG, Basel. |
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Chotjumlong P. Bolscher J.G. Nazmi K. Reutrakul V. Supanchart C. Buranaphatthana W. Krisanaprakornkit S. |
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Chotjumlong P. Bolscher J.G. Nazmi K. Reutrakul V. Supanchart C. Buranaphatthana W. Krisanaprakornkit S. Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
author_facet |
Chotjumlong P. Bolscher J.G. Nazmi K. Reutrakul V. Supanchart C. Buranaphatthana W. Krisanaprakornkit S. |
author_sort |
Chotjumlong P. |
title |
Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
title_short |
Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
title_full |
Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
title_fullStr |
Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
title_full_unstemmed |
Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37 |
title_sort |
involvement of the p2x7 purinergic receptor and c-jun n-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin e2 induction by ll-37 |
publishDate |
2014 |
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http://www.scopus.com/inward/record.url?eid=2-s2.0-84872276132&partnerID=40&md5=ea2e6c670e2a54ef354c160f0b18cd68 http://cmuir.cmu.ac.th/handle/6653943832/4019 |
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