Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL-1) in normal human gingival fibroblasts

Lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL-1) activate human gingival fibroblasts to induce IL-6 production and ICAM-1 expression. Human gingival fibroblasts were treated with lipoproteins or FSL-1 and then examined for the activation of mitogen-activated protein kinases (MAPKs), ERK1/2, p38, and SAPK/JNK, and transcription factors, AP-1 and NF-kappaB. Western blotting indicated that p38 and SAPK/JNK were activated in response to the stimulators, but the activation of ERK1/2 could not be discriminated because ERK1/2 was activated in the absence of stimulators. The p38 inhibitor SB 203580 also suppressed their IL-6 production-inducing activities, whereas the ERK1/2-activating MAPK kinase (MEK1) inhibitor PD 98059 did not suppress their activities. Moreover, they were capable of inducing the activation of AP-1 and NF-kappaB. NF-kappaB activation was also confirmed by the phosphorylation of IkappaB-alpha. On the basis of these results, it was concluded that lipoproteins of M. salivarium and FSL-1 are capable of activating the MAPKs p38 and SAPK/JNK and the transcriptional factors AP-1 and NF-kappaB in human gingival fibroblasts.