Mixed Periodontal Th1-Th2 Cytokine Profile in Actinobacillus actinomycetemcomitans -Specific Osteoprotegerin Ligand (or RANK-L)- Mediated Alveolar Bone Destruction In Vivo

Abstract

The Th1/Th2 cytokines involved in human periodontitis remain unclear; therefore, we established a humanized mouse model to investigate this issue in Actinobacillus actinomycetemcomitans-mediated periodontal infection. Quantitative-PCR analysis clearly demonstrates a predominantly mixed Th1 and Th2 expression profile associated with pathogen-specific cell-mediated immunity via osteoprotegerin ligand (or RANK-L)-mediated alveolar bone destruction in vivo.

The Cytolethal Distending Toxin Induces Receptor Activator of NF-κB Ligand Expression in Human Gingival Fibroblasts and Periodontal Ligament Cells

“…Alternatively, the possibility exists that RANKL is expressed by infiltrating activated T lymphocytes (23,52). This is demonstrated by the finding that A. actinomycetemcomitans antigen-specific Th1 cells obtained from experimental periodontitis rats express higher levels of RANKL compared to the healthy controls (59) and further supported by the finding that A. actinomycetemcomitans extract enhances RANKL mRNA expression in CD4 ϩ T-lymphocytes (54,55). We show here that A. actinomycetemcomitans stimulates RANKL mRNA and protein expression in periodontal connective tissue cells as well.…”

“…Therefore, the direct interaction of diffused toxins with cells of the periodontal tissues may induce the expression of molecules related to osteoclastogenesis at the front of alveolar bone resorption. In experimental periodontitis models, profound alveolar bone loss can be caused by transplantation of A. actinomycetemcomitans antigen-specific Th1 cells in rats (19,59) or by transplantation of blood mononuclear leukocytes from patients with localized aggressive periodontitis to NOD/SCID mice and intraoral inoculation with A. actinomycetemcomitans (54,55). Previous studies have demonstrated that proteinaceous surface-associated components (22, 32, 41, 42, 61) or the LPS …”

Tight-adherence genes of Actinobacillus actinomycetemcomitans are required for virulence in a rat model

“…Among other important variations that could affect conclusions drawn from animal models, nonhuman animals differ from humans in anatomy, immune response, and lifestyle. For the study of periodontal disease, mice (25,33,34,(37)(38)(39), rats (36,40,41), and nonhuman primates (42)(43)(44) have been most frequently used. While primates closely resemble humans with regard to anatomy and physiology, their cost, size, and maintenance requirements prohibit studies with large samples.…”

Interleukin-10 Inhibits Gram-Negative-Microbe-Specific Human Receptor Activator of NF-κB Ligand-Positive CD4 + -Th1-Cell- Associated Alveolar Bone Loss In Vivo

“…ϩ Th cells in vivo and (ii) increased hIFN-␥ coexpression in pathogen-reactive RANKL ϩ Th cells is associated with elevated alveolar bone loss (19,30,32). In this study, to assess the effects of an anti-inflammatory cytokine on RANKL ϩ Th cells coexpressing hIFN-␥ during periodontal pathogenesis, we injected hIL-10 (200 ng/mouse, administered intraperitoneally; 50 to 250 ng tested; BD Pharmingen) (32) or phosphate-buffered saline (sham control) into A. actinomycetemcomitans-infected HuPBL-NOD/SCID mice (five or six mice/human peripheral blood leukocyte [HuPBL] donor/ group) twice a week for the first 3 weeks, as described previ-ously (30,32).…”

“…In this study, to assess the effects of an anti-inflammatory cytokine on RANKL ϩ Th cells coexpressing hIFN-␥ during periodontal pathogenesis, we injected hIL-10 (200 ng/mouse, administered intraperitoneally; 50 to 250 ng tested; BD Pharmingen) (32) or phosphate-buffered saline (sham control) into A. actinomycetemcomitans-infected HuPBL-NOD/SCID mice (five or six mice/human peripheral blood leukocyte [HuPBL] donor/ group) twice a week for the first 3 weeks, as described previ-ously (30,32). Briefly, a total of 82 6-to-8-week-old female NOD/SCID mice were housed under specific-pathogen-free conditions at the University Animal Colony Facilities.…”