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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Apical periodontitis (periapical lesions) is an infection-induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll-like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2/TLR4 double deficient (dKO), and wild-type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection-induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF-kB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency-dependent elevation of CD14 (cluster of differentiation 14), which is a co-receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency-dependent inflammation and tissue destruction in vitro and in vivo. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction. Anat Rec, 299:1281–1292, 2016.

Original languageEnglish
Pages (from-to)1281-1292
Number of pages12
JournalAnatomical Record
Volume299
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • CD14
  • apical periodontitis
  • inflammation
  • innate immunity
  • toll-like receptor (TLR)

ASJC Scopus subject areas

  • Anatomy
  • Biotechnology
  • Histology
  • Ecology, Evolution, Behavior and Systematics

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    Rider, D., Furusho, H., Xu, S., Trachtenberg, A. J., Kuo, W. P., Hirai, K., Susa, M., Bahammam, L., Stashenko, P., Fujimura, A., & Sasaki, H. (2016). Elevated CD14 (Cluster of Differentiation 14) and Toll-Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice. Anatomical Record, 299(9), 1281-1292. https://doi.org/10.1002/ar.23383