title: Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated genes following stimulation with Porphyromonas gingivalis.
abstract: OBJECTIVE
  Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease, including socio-economic status, genetics and age; however, inflammation elicited by the presence of specific bacteria in the subgingival space is thought to drive the majority of soft- and hard-tissue destruction. Porphyromonas gingivalis is closely associated with periodontal disease. Toll-like receptors (TLRs) and their intracellular signaling pathways play roles in the host response to P. gingivalis. The focus of the current study was to use microarray analysis to define the contributions of the TLR adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/interleukin-1 receptor domain-containing adaptor inducing interferon-beta (TRIF), and aging, on the expression of TLR pathway-associated mRNAs in response to P. gingivalis.
  
  
  METHODS
  Bone marrow-derived macrophages (BMØ) from wild-type (Wt), MyD88 knockout (MyD88-KO) and Trif(Lps2) [i.e. containing a point mutation in the lipopolysaccharide 2 (Lps2) gene rendering the Toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-beta (TRIF) protein nonfunctional] mice, at 2-and 12-mo of age, were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison with expression of genes in BMØ cultured in medium only.
  
  
  RESULTS
  Using, as criteria, a twofold increase or decrease in mRNA expression, differential expression of 32 genes was observed when Wt BMØ from 2-mo-old mice were cultured with P. gingivalis compared with the medium-only control. When compared with 2-mo-old Wt mice, 21 and 12 genes were differentially expressed (p < 0.05) as a result of the mutations in MyD88 or TRIF, respectively. The expression of five genes was significantly (p < 0.05) reduced in Wt BMØ from 12-mo-old mice compared with those from 2-mo-old mice following culture with P. gingivalis. Age also influenced the expression of genes in MyD88-KO and Trif(Lps2) mice challenged with P. gingivalis.
  
  
  CONCLUSIONS
  Our results indicate that P. gingivalis induces differential expression of TLR pathway-associated genes, and both MyD88 and TRIF play roles in the expression of these genes. Age also played a role in the expression of TLR-associated genes following stimulation of BMØ with P. gingivalis.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University Medical Center, Boston, MA, USA.
authors.forename: Y B
authors.initials: YB
authors.lastname: Shaik-Dasthagirisaheb
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: E O
authors.initials: EO
authors.lastname: Weinberg
authors.forename: S S
authors.initials: SS
authors.lastname: Shen
authors.forename: C A
authors.initials: CA
authors.lastname: Genco
authors.forename: F C
authors.initials: FC
authors.lastname: Gibson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse
keywords: Porphyromonas gingivalis; Toll/interleukin-1 receptor domain-containing adaptor inducing interferon-beta; innate immunity; mRNA expression; macrophage; myeloid differentiation factor 88; toll-like receptors