Aging and contribution of MyD88 and TRIF to expression of TLR pathway‐associated genes following stimulation with Porphyromonas gingivalis

Abstract

BACKGROUND AND OBJECTIVE Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease including socioeconomic status, genetics, 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 host responses to P. gingivalis. The focus of current study was to use microarray analysis to define the contributions that TLR adaptor molecules MyD88 and TRIF, and aging have on TLR pathway associated mRNA expression in response to P. gingivalis. MATERIALS AND METHODS Bone marrow derived macrophages (BMØ) from wild type (Wt), MyD88-KO and TrifLps2 mice at 2-months and 12-months of age were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison to medium alone control. RESULTS Using a two-fold cut-off in mRNA expression criteria, differential expression of 32 genes was observed when Wt BMØ from 2-month old mice were cultured with P. gingivalis compared with medium alone control. When compared with 2-month old Wt, 21 and 12 genes were differentially expressed (P<0.05) as a result of MyD88 or TRIF mutations respectively. The expression of 5 genes was significantly (P<0.05) reduced in the 12-month group compared to the 2-month group in Wt BMØ following culture with P. gingivalis. Age also influenced expression of genes in MyD88-KO and TrifLps2 mice challenged with P. gingivalis. CONCLUSION 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.

Age‐related changes in immune function (immune senescence) in caries and periodontal diseases: a systematic review

“…), whereas reduced expression of TLR‐pathway‐associated genes was noted in bone marrow‐derived macrophages of older mice compared to younger mice (Shaik‐Dasthagirisaheb et al. ).…”

“…There was also evidence of a trend for reduced expression of TLR‐pathway‐associated genes and genes involved in intracellular signalling in older mice (Shaik‐Dasthagirisaheb et al. ). Similarly, in a study in which mouse gingival fibroblasts were challenged with P. gingivalis , a variable pattern of increased and decreased gene expression was again noted when comparing young and older mice.…”

Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways

“…In our study, oxLDL-induced DPP4 upregulation was even slightly enhanced in MyD88 deficient macrophages. This could be a result of the compensatory enhancement of TRIF signaling in MyD88 knockout macrophages [48]. The role of TRIF signaling in atherosclerosis is complex.…”

Management of patients with flail chest by surgical fixation using claw-type titanium plate

“…Moreover, long-term observation on the outcome of patients undergoing surgical fixation for rib fractures reveals that up to 90 % of the involved patients are able to return to work with few limitation at about 2 months postoperatively [ 12 ]. The National Institute for Health and Clinical Excellence recommendations in Britain has recommended surgical rib fixation in the management of patients with severe fractures [ 13 ]. A study suggests potential indications for operative repair of fractured ribs, such as flail chest, painful, movable rib fractures resistant to conservative pain management and rib fracture nonunion [ 14 ].…”