Nuclear factor-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

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.gingivalis LPS 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.gingivalis LPS differently modulate the immuno-inflammatory response, and P.gingivalis LPS1690 induces LBP expression in human oral keratinocytes (HOKs). This study further examined the signaling mechanisms of P.gingivalis LPS1690-induced and Escherichia coli LPS-induced LBP expression in HOKs. Both P.gingivalis LPS1690 and E.coli LPS were potent inducers of LBP expression in HOKs. The former activated phosphorylation of IB, p65, p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), whereas the latter phosphorylated IB, p38 MAPK and SAPK/JNK. A nuclear translocation of NF-B transcription factor was confirmed upon stimulation by both forms of LPS. Further blocking assay showed that P.gingivalis LPS1690 induction of LBP was through NF-B and p38 MPAK pathways, whereas E.coli LPS-induced LBP expression was mediated by NF-B, p38 MPAK and JNK pathways. This study demonstrates that NF-B and p38 MAPK signaling pathways are involved in P.gingivalis LPS1690 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.