Elevated CD14 (Cluster of Differentiation 14) and Toll‐Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice

Rider, Daniel; Furusho, Hisako; Xu, Shuang; Trachtenberg, Alexander J.; Kuo, Winston Patrick; Hirai, Kazumasa; Susa, Mako; Bahammam, Laila; Stashenko, Philip; Fujimura, Akiko; Sasaki, Hajime

doi:10.1002/ar.23383

Cited by 21 publications

(25 citation statements)

References 39 publications

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“…On the other hand, the TLR4 signaling depends on other co-receptors such as CD14, LBP, and MD2 2 , 10 , 22 . According to Rider, et al 24 (2016), TLR2 signaling is an endogenous suppressor of cellular CD14 expression. This mechanism prevents overactive CD14/TLR4-mediated inflammation against microbial infection.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and mRNA expression of RANK, RANKL, OPG, TLR2 and MyD88 during apical periodontitis progression in mice

et al. 2018

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Objective To evaluate and correlate, in the same research, the mRNA expression and the staining of RANK, RANKL, OPG, TLR2 and MyD88 by immunohistochemistry in the apical periodontitis (AP) progression in mice.Material and Methods AP was induced in the lower first molars of thirty-five C57BL/6 mice. They were assigned to four groups according to their euthanasia periods (G0, G7, G21 and G42). The jaws were removed and subjected to histotechnical processing, immunohistochemistry and real-time reverse transcription-PCR (qRT-PCR). Data were analyzed with parametric and nonparametric tests (α=0.05).Results An increase of positive immunoreactivity for RANK, RANKL, OPG, TLR2 and MyD88 was observed over time (p<0.05). The RANKL expression was different between the groups G0 and G42, G21 and G42 (p=0.006), with G42 presenting the higher expression in both comparations. The OPG expression was statistically different between the groups G0 and G7, G7 and G21 and G7 and G42 (p<0.001), with G7 presenting higher expression in all the time points. The TLR2 expression was different between the groups G0 and G42 (p=0.03), with G42 showing the higher expression. The MyD88 expression presented a statistical significant difference between groups G7, G21 and G42 compared with G0 (p=0.01), with G0 presenting the smallest expression in all the comparisons. The Tnfrsf11/Tnfrsf11b (RANKL/OPG) ratio increased with the AP progression (p=0.002). A moderate positive correlation between MyD88 and RANKL (r=0.42; p=0.03) and between MyD88 and TLR2 (r=0.48; p<0.0001) was observed.Conclusion The expression of the RANK, RANKL, OPG, MyD88 and TLR2 proteins as well as the ratio Tnfrsf11/Tnfrsf11b (RANKL/OPG) increased with AP progression. There was also a moderate positive correlation between the expression Myd88-Tnfrsf11 and Tlr2-Myd88, suggesting the relevance of Tlr2-Myd88 in bone loss due to bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical and mRNA expression of RANK, RANKL, OPG, TLR2 and MyD88 during apical periodontitis progression in mice

et al. 2018

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“…The study was reviewed and approved by the institutional ethics committee of Tokyo Medical and Dental University (approval D2014-039). Animals SAA1.1/2.1 double knockout (dKO; de Beer et al 2010), SAA3 knockout (KO), TLR2 KO, TLR4 KO (Hoshino et al 1999), and TLR2/4 dKO (Rider et al 2016) mice were employed in this study. Frozen sperm of the SAA3 KO strain and breeding pairs of TLR2 KO mice (B6.129-Tlr2 tm1Kir /J) were purchased from the Knockout Mouse Project at the University of California-Davis and The Jackson Laboratory, respectively.…”

Section: Human Periapical Surgical Specimensmentioning

confidence: 99%

Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4

et al. 2018

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In the current concept of bacterial infections, pathogen-associated molecular patterns (PAMPs) derived from pathogens and damage-associated molecular patterns (DAMPs) released from damaged/necrotic host cells are crucial factors in induction of innate immune responses. However, the implication of DAMPs in apical and marginal periodontitis is unknown. Serum amyloid A (SAA) is a DAMP that is involved in the development of various chronic inflammatory diseases, such as rheumatoid arthritis. In the present study, we tested whether SAA is involved in the pathogenesis of periapical lesions, using human periapical surgical specimens and mice deficient in SAA and Toll-like receptors (TLR). SAA1/2 was locally expressed in human periapical lesions at the mRNA and protein levels. The level of SAA protein appeared to be positively associated with the inflammatory status of the lesions. In the development of mouse periapical inflammation, SAA1.1/2.1 was elevated locally and systemically in wild-type (WT) mice. Although SAA1.1/2.1 double-knockout and SAA3 knockout mice had redundant attenuation of the extent of periapical lesions, these animals showed strikingly improved inflammatory cell infiltration versus WT. Recombinant human SAA1 (rhSAA1) directly induced chemotaxis of WT neutrophils in a dose-dependent manner in vitro. In addition, rhSAA1 stimulation significantly prolonged the survival of WT neutrophils as compared with nonstimulated neutrophils. Furthermore, rhSAA1 activated the NF-κB pathway and subsequent IL-1α production in macrophages in a dose-dependent manner. However, TLR2/TLR4 double deficiency substantially diminished these SAA-mediated proinflammatory responses. Taken together, the SAA-TLR axis plays an important role in the chronicity of periapical inflammation via induction of inflammatory cell infiltration and prolonged cell survival. The interactions of PAMPs and DAMPs require further investigation in dental/oral inflammation.

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“…TLRs recognize pathogen-associated molecular patterns (PAMPs), such as bacterial or viral components, and endogenous mediators, such as proteins and proinflammatory cytokines (3). Previous studies in experimental animals (4)(5)(6) and in humans (7) have demonstrated that TLRs play an important role in the AP pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

MMP2 and MMP9 are Associated with Apical Periodontitis Progression and Might be Modulated by TLR2 and MyD88

et al. 2018

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The aim of this study was to evaluate the expression of MMP2 and MMP9 during apical periodontitis (AP) progression in TLR2 (TLR2 KO) and in MyD88 (MyD88 KO) knockout mice compared to wild type (WT) mice. AP was induced in mandibular first molars of TLR2 KO (n= 18), MyD88 KO (n= 18), and WT mice (n= 18). After 7, 21, and 42 days, the animals were euthanized and the jaws were dissected and subjected to histotechnical processing. Subsequent sections were stained by immunohistochemistry and evaluated for detection of MMP2 and MMP9. Statistical analysis of the semi-quantitative analysis of immunohistochemistry was performed using chi-square test (α = 0.05). In the initial periods of AP progression, an increased expression of MMP9 in the TLR2 KO and MyD88 KO mice was observed. In the final periods of AP progression, a reduction of MMP2 expression and an increase of MMP9 expression in the TLR2 KO mice were observed. MMP2 and MMP9 production was modulated for TLR2 and MyD88 during apical periodontitis progression. MMP2 and MMP9 are Associated w i t h A p i c a l P e r i o d o n t i t i s P r o g r e s s i o n a n d M i g h t b e Modulated by TLR2 and MyD88

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Elevated CD14 (Cluster of Differentiation 14) and Toll‐Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice

Cited by 21 publications

References 39 publications

Immunohistochemical and mRNA expression of RANK, RANKL, OPG, TLR2 and MyD88 during apical periodontitis progression in mice

Immunohistochemical and mRNA expression of RANK, RANKL, OPG, TLR2 and MyD88 during apical periodontitis progression in mice

Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4

MMP2 and MMP9 are Associated with Apical Periodontitis Progression and Might be Modulated by TLR2 and MyD88

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