Nuclear factor-[kappa]B and p38 mitogen-activated protein kinase signaling pathways are critically involved in Porphyromonas gingivalis lipopolysaccharide induction of lipopolysaccharide-binding protein expression in human oral keratinocytes

• Published in: Molecular oral microbiology Vol. 28; no. 2; p. 129
• Main Authors: Ding, P-H, Wang, C-Y, Darveau, RP, Jin, LJ
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01-04-2013
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12010

Summary Lipopolysaccharide (LPS) -binding protein (LBP) plays a crucial role in innate host response to bacterial challenge. Porphyromonas gingivalis is a keystone pathogen in periodontal disease and the shift of P. gingivalisLPS lipid A structure from penta-acylated (LPS1690) to tetra-acylated (LPS1435/1449) isoform may significantly contribute to periodontal pathogenesis. We recently demonstrated that LBP is expressed in human gingiva and contributes to periodontal homeostasis. Furthermore, different isoforms of P. gingivalisLPS differently modulate the immuno-inflammatory response, and P. gingivalisLPS1690 induces LBP expression in human oral keratinocytes (HOKs). This study further examined the signaling mechanisms of P. gingivalisLPS1690-induced and Escherichia coliLPS-induced LBP expression in HOKs. Both P. gingivalisLPS1690 and E. coliLPS were potent inducers of LBP expression in HOKs. The former activated phosphorylation of I[kappa]B[alpha], p65, p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), whereas the latter phosphorylated I[kappa]B[alpha], p38 MAPK and SAPK/JNK. A nuclear translocation of NF-[kappa]B transcription factor was confirmed upon stimulation by both forms of LPS. Further blocking assay showed that P. gingivalisLPS1690 induction of LBP was through NF-[kappa]B and p38 MPAK pathways, whereas E. coliLPS-induced LBP expression was mediated by NF-[kappa]B, p38 MPAK and JNK pathways. This study demonstrates that NF-[kappa]B and p38 MAPK signaling pathways are involved in P. gingivalisLPS1690 induction of LBP expression in HOKs. The current findings could enhance the understanding of the molecular mechanisms of innate defense in maintenance of periodontal homeostasis.