RRC ID 6573
著者 Ohno T, Okahashi N, Morisaki I, Amano A.
タイトル Signaling pathways in osteoblast proinflammatory responses to infection by Porphyromonas gingivalis.
ジャーナル Oral Microbiol Immunol
Abstract INTRODUCTION:We recently investigated global gene expression in ST2 mouse stromal cells infected by the periodontal pathogen Porphyromonas gingivalis using microarray technology, and found that the bacterium induces a wide range of proinflammatory gene expression. Here, we reported the signaling pathways involved in those proinflammatory responses.
METHODS:ST2 cells and primary calvarial osteoblasts from C3H/HeN, C57BL/6, and MyD88-deficient (MyD88(-/-)) mice were infected with P. gingivalis ATCC33277 and its gingipain-deficient mutant KDP136. Expression of the chemokines CCL5 and CXCL10, and matrix metalloproteinase-9 (MMP9) were quantified by real-time polymerase chain reaction, while phosphorylation of protein kinases and degradation of an inhibitor of nuclear factor-kappaB, IkappaB-alpha, were detected by Western blotting, and activation of transcriptional factors was determined by a luciferase reporter assay. The effects of inhibitors of transcriptional factors and protein kinases were also investigated.
RESULTS:Infection by P. gingivalis elicited gene expression of CCL5, CXCL10, and MMP9 in both ST2 cells and osteoblasts. Western blot and reporter assay results revealed activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 transcription factors. The NF-kappaB inhibitor suppressed the expression of CCL5 and MMP9, but not that of CXCL10, whereas P. gingivalis infection induced significant CCL5 expression in MyD88(-/-) osteoblasts. In addition, activation of protease-activated receptors by trypsin elicited significant induction of CXCL10.
CONCLUSION:Our results suggest that various proinflammatory responses in P. gingivalis-infected stromal/osteoblast cells are NF-kappaB-dependent, but not always dependent on the Toll-like receptor/MyD88 pathway, while some responses are related to the activation of protease-activated receptors. Thus, P. gingivalis does not fully utilize well-established pathogen recognition molecules such as Toll-like receptors.
巻・号 23(2)
ページ 96-104
公開日 2008-4-1
DOI 10.1111/j.1399-302X.2007.00393.x
PII OMI393
PMID 18279176
MeSH Animals Blotting, Western Bone Marrow Cells / metabolism Bone Marrow Cells / microbiology Cell Line Chemokine CCL5 / biosynthesis* Chemokine CXCL10 / biosynthesis* Inflammation / metabolism* Matrix Metalloproteinase 9 / biosynthesis* Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88 / metabolism NF-kappa B / metabolism* Osteoblasts / metabolism* Osteoblasts / microbiology* Porphyromonas gingivalis / physiology* Signal Transduction* Stromal Cells / metabolism Stromal Cells / microbiology Transcription Factor AP-1 / metabolism
引用数 16
WOS 分野 DENTISTRY, ORAL SURGERY & MEDICINE IMMUNOLOGY MICROBIOLOGY
リソース情報
ヒト・動物細胞