Stimulation of IL-6 cytokines in fibroblasts by toll-like receptors 2.
The osteotropic interleukin-6 (IL-6) types of cytokines IL-6, IL-11, and leukemia inhibitory factor (LIF), but not oncostatin M, are expressed by human gingival fibroblasts, and their expressions are regulated by IL-1 and tumor necrosis factor-alpha (TNF-alpha). In the present study, we investigated whether signaling through Toll-like receptor 2 (TLR2) can affect the expression of these cytokines in human gingival fibroblasts. Lipopolysac-charide (LPS) from P. gingivalis was found to stimulate IL-6 and LIF mRNA and protein, but not IL-11 or OSM mRNA. Using two synthetic ligands acting specifically at TLR2 and siRNA knockdown of TLR2, we demonstrated the important role of TLR2 in the stimulation of IL-6 and LIF in gingival fibroblasts. Analysis of these data suggests that signaling through the innate immune system controls the expression of osteotropic cytokines in human gingival fibroblasts.
Souza
P P C
PP
Department of Oral Cell Biology, Umeå University, 901 87 Umeå, Sweden.
Palmqvist
P
P
Lundgren
I
I
Lie
A
A
Costa-Neto
C M
CM
Lundberg
P
P
Lerner
U H
UH
D000704:Analysis of Variance; D001862:Bone Resorption / Q000503:physiopathology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000378:metabolism; D018709:Statistics, Nonparametric; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology
D017370:Interleukin-11; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4