MspTL is the major surface protein of Treponema lecithinolyticumassociated with periodontitis and endodontic infections.Our recent investigation revealed that MspTL inducesproinflammatory cytokines and intercellular adhesion molecule1 in THP-1 cells and periodontal ligament cells. In thisstudy we conducted oligonucleotide microarray analysis toinvestigate the global transcriptional regulation in THP-1cells stimulated with purified recombinant MspTL. MspTLupregulated the expression of 90 genes in THP-1 cells at leastfour fold, and the functions of these genes were categorizedinto adhesion, apoptosis/antiapoptosis, cell cycle/growth/differentiation,chemotaxis, cytoskeleton organization, immuneresponse, molecular metabolism, proteolysis, signaling, andtranscription. The majority of the modified genes are knownto be NF-κB-responsive and interferon-stimulated genes(ISGs). The expression of 12 selected genes was confirmed byreal-time RT-PCR. Because prostaglandin E2 (PGE2) is animportant inflammatory mediator and Cox-2 was found tobe induced by MspTL in the microarray analysis, wedetermined the level of PGE2 in the culture supernatants ofMspTL-treated cells and found that MspTL significantlyincreased PGE2. Our results provide insight into the generegulation of host cells in response to MspTL, and maycontribute to the understanding of the molecular mechanismin periodontitis.