Proinflammatory gene expression in mouse ST2 cell line in response to infection by Porphyromonas gingivalis.
Porphyromonas gingivalis is a predominant periodontal pathogen, whose infection causes inflammatory responses in periodontal tissue and alveolar bone resorption. Various virulence factors of this pathogen modulate host innate immune responses. It has been reported that gingipains degrade a wide variety of host cell proteins, and fimbriae are involved in bacterial adhesion to and invasion of host cells. In the present study, we profiled ST2 stromal cell gene expression following infection with the viable P. gingivalis strain ATCC33277 as well as with its gingipain- and fimbriae-deficient mutants, using microarray technology and quantitative real-time polymerase chain reaction. Using a mouse array of about 20,000 genes, we found that infection with the wild strain elicited a significant upregulation (greater than 2-fold) of expression of about 360 genes in ST2 cells, which included the chemokines CCL2, CCL5, and CXCL10, and other proinflammatory proteins such as interleukin-6 (IL-6) and matrix metalloproteinase-13 (MMP-13). Further, infection with the gingipain-deficient mutant elicited a reduced expression of the CXCL10, IL-6 and MMP-13 genes, suggesting that gingipains play an important role in inducing the expression of those genes following P. gingivalis infection. On the other hand, the pattern of global gene expression induced by the fimbriae-deficient mutant was similar to that by the wild strain. These results suggest that P. gingivalis infection induces gene expression of a wide variety of proinflammatory proteins in stromal cells/osteoblasts, and gingipains may be involved in inducing several of the proinflammatory factors.
Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
Takashi
T
Ohno
Nobuo
N
Okahashi
Shinji
S
Kawai
Takahiro
T
Kato
Hiroaki
H
Inaba
Yasuko
Y
Shibata
Ichijiro
I
Morisaki
Yoshimitsu
Y
Abiko
Atsuo
A
Amano
D018829:Adhesins, Bacterial / Q000235:genetics; D000818:Animals; D016866:Bacteroidaceae Infections / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005796:Genes / Q000235:genetics*; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000235:genetics; D053509:Matrix Metalloproteinase 13; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016966:Porphyromonas gingivalis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation
D018829:Adhesins, Bacterial; D016207:Cytokines; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse