Involvement of the P2X<inf>7</inf>purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E<inf>2</inf>induction by LL-37

• Main Authors: Pareena Chotjumlong, Jan G. Bolscher, Kamran Nazmi, Vichai Reutrakul, Chayarop Supanchart, Worakanya Buranaphatthana, Suttichai Krisanaprakornkit
• Format: Journal
• Published: 2018
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84872276132&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/48338
• Institution: Chiang Mai University

Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E 2 (PGE 2 ) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE 2 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 PGE 2 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 PGE 2 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 P2X 7 purinergic receptor significantly abrogated COX-2 induction and PGE 2 production by LL-37 (p < 0.01). LL-37 upregulated COX-2 expression and PGE 2 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 PGE 2 synthesis via the P2X 7 receptor, ERK, and p46 JNK. The pro-inflammatory effects of LL-37 may be essential for initiating oral mucosal inflammation in periodontal disease. Co pyright © 2012 S. Karger AG, Basel.