In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria. Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone. This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] which are involved in bone resorption. We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens. We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen. Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days. At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting. Cytokine mRNA was not detected in the tissue over the calvaria of control animals. In contrast, P. gingivalis and A. actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6). P. gingivalis was more potent than A. actinomycetemcomitans in inducing cytokine expression. In contrast, S. gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction. These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines. There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues.
Kesavalu
L
L
Department of Oral Health Science, Center for Oral Health Research, College of Dentistry 159 HSRB, University of Kentucky, Lexington, KY 40536-0305, USA.
Chandrasekar
B
B
Ebersole
J L
JL
D000189:Actinobacillus Infections / Q000378:metabolism; D016976:Aggregatibacter actinomycetemcomitans / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D016866:Bacteroidaceae Infections / Q000378:metabolism; D015152:Blotting, Northern; D001862:Bone Resorption / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000378:metabolism; D010294:Parietal Bone / Q000378:metabolism / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012886:Skull / Q000378:metabolism / Q000382:microbiology; D013291:Streptococcus / Q000145:classification / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha