Actinobacillus actinomycetemcomitans Y4 capsular polysaccharide induces IL-1beta mRNA expression through the JNK pathway in differentiated THP-1 cells.
Capsular polysaccharide from Actinobacillus actinomycetemcomitans Y4 (Y4 CP) induces bone resorption in a mouse organ culture system and osteoclast formation in mouse bone marrow cultures, as reported in previous studies. We also found that Y4 CP inhibits the release of interleukin (IL)-6 and IL-8 from human gingival fibroblast (HGF). Thus Y4 CP induces various responses in localized tissue and leads to the secretion of several cytokines. However, the effects of Y4 CP on human monocytes/macrophages are still unclear. In this study, THP-1 cells, which are a human monocytic cell line, were stimulated with Y4 CP, and we measured gene expression in inflammatory cytokine and signal transduction pathways. IL-1beta and tumour necrosis factor (TNF)-alpha mRNA were induced from Y4 CP-treated THP-1 cells. IL-1beta mRNA expression was increased according to the dose of Y4 CP, and in a time-dependent manner. IL-1beta mRNA expression induced by Y4 CP (100 microg/ml) was approximately 7- to 10-fold greater than that in the control by real-time PCR analysis. Furthermore, neither PD98059, a specific inhibitor of extracellular signal-regulated kinase nor SB203580, a specific inhibitor of p38 kinase prevented the IL-1beta expression induced by Y4 CP. However, JNK Inhibitor II, a specific inhibitor of c-Jun N-terminal kinase (JNK) prevented the IL-1beta mRNA expression induced by Y4 CP in a concentration-dependent manner. These results indicate that Y4 CP-mediated JNK pathways play an important role in the regulation of IL-1beta mRNA. Therefore, Y4 CP-transduced signals for IL-1beta induction in the antibacterial action of macrophages may provide a therapeutic strategy for periodontitis.
Iwata
T
T
Department of Periodontology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8651, Japan.
Mitani
A
A
Ishihara
Y
Y
Tanaka
S
S
Yamamoto
G
G
Kikuchi
T
T
Naganawa
T
T
Matsumura
Y
Y
Suga
T
T
Koide
M
M
Sobue
T
T
Suzuki
T
T
Noguchi
T
T
D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C015482:protein kinase modulator; D048031:JNK Mitogen-Activated Protein Kinases