Interleukin (IL)-6, IL-8 and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts is regulated by both MyD88 and TRAM
Ana C. Morandini: 0000-0003-4749-571X
EUROPERIO 7 - 7th Conference of the European Federation of Periodontology
European Federation of Periodontology
June 6-9, 2012
Date of Presentation
Aim: Fibroblasts are now seen as active components of the immune response because these cells express Toll-like receptors (TLRs), recognize periodontopathogens and mediate cytokines and chemokines production during inflammation. This study investigated whether knocking down two important TLRs adaptor molecules such as myeloid differentiation protein (MyD88) and TRIF-related adaptor molecule (TRAM) could affect mRNA expression of Interleukin (IL)-6, IL-8 and CXCL12 in human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPLF).
Material and Methods: After small interfering RNA-mediated silencing of MyD88 and TRAM, HGF and HPLF were stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS), Escherichia coli LPS, and two synthetic ligands of TLR2 (Pam2CSK4 and Pam3CSK4) for 6 hours. IL-6, IL-8 and CXCL12 mRNA levels were evaluated by qRT-PCR.
Results: Knockdown of MyD88 and TRAM decreased IL-6 and IL-8 mRNA levels in response to all stimuli in both fibroblasts subpopulations, but mainly in HGF. On the other hand, CXCL12 mRNA levels were upregulated by MyD88 and TRAM knockdown in HGF, but for HPLF it remained unchanged by both TLRs adaptor molecules silencing.
Conclusion: These results suggest that knocking down TLRs adaptor molecules, such as MyD88 and TRAM can decrease IL-6 and IL-8 mRNA expression and increase CXCL12, in HGF and HPLF. This can be an important step for the better understanding of the mechanisms that control the inflammatory cytokines and chemokines release which in turn contribute to periodontal pathogenesis.
Morandini, A. C.,
Souza, P. P.,
Ramos-Junior, E. S.,
Sipert, C. R.,
Souza Costa, C. A.,
Santos, C. F.
Interleukin (IL)-6, IL-8 and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts is regulated by both MyD88 and TRAM.
Paper presented at EUROPERIO 7 - 7th Conference of the European Federation of Periodontology in Vienna, Austria.