50 TLR2 Signal Is Protective In Periapical Lesion

Wednesday, March 21, 2012: 2:30 p.m. - 4 p.m.
Presentation Type: Oral Session
H. SASAKI1, D. RIDER1, S. XU1, and A. FUJIMURA2, 1Forsyth Institute, Cambridge, MA, 2Iwate Medical University, Morioka, Japan
Objective: We previously reported that TLR4 signal, which is triggered by Gram-negative bacteria, mediates infection-induced periapical bone loss. Although TLR2 triggers inflammation in response to Gram-positive bacteria, the role of TLR2 in periapical inflammation is still unclear. In the present study, we determined the functional role of TLR2 signal in polymicrobial infection-induced periapical bone loss using TLR gene deficient (-/-) mice.

Method: TLR2-/-, TLR2/TLR4-/-, and C57BL/6 (WT) mice were employed. The dental pulps of the first molars were exposed and infected with a mixture of Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros, and Streptococcus intermedius. Mice were sacrificed on days 0 (non-infected control) and 21 after pulpal infection. The extent of periapical bone loss was determined using micro computed tomography. Thioglycolate-elicited peritoneal macrophages were isolated from the mice above and stimulated with or without E. coli LPS (1µg/ml) and Pam2CSK4 (100ng/mL) for 16 hrs. Gene expression in macrophages was assessed by quantitative RT-PCR.

Result: The extent of infection-induced periapical bone loss in TLR2-/- mice was significantly higher than other two strains on day 21 after pulpal infection (>2-fold; p<0.01), suggesting TLR2 signal appears to be protective in the development of periapical lesion. Since the extent of bone loss was similar in TLR2/TLR4-/- and WT mice, the extended bone loss in TLR2-/- seems to be mediated by TLR4 signal. In response to LPS/Pam2CSK4 stimulation, TLR4 signaling pathway including CD14, IRAK2, and RelB, but not TLR4, was significantly up-regulated in TLR2-/- macrophages vs. WT cells (p<0.05). This finding suggests that signal cross-talk between TLR2 and TLR4 seems to regulate CD14/TLR4 complex formation and subsequent TLR4 signal.

Conclusion: TLR2 signal seems to be protective via suppression of TLR4 signal in the development of periapical bone loss.

This abstract is based on research that was funded entirely or partially by an outside source: NATIONAL CENTER FOR RESEARCH RESOURCES/NATIONAL INSTITUTES OF HEALTH 1S10RR027553-01

Keywords: Animal, Bone, Endodontics, Immune response and Resorption