repeats a transmembrane region and a cytoplasmic region that contains a Toll/interleukin receptor domain [14] The cellular localization of TLR3 varies by cell type; it can be found on the surface of the cell membrane or on intracellular lysosomal membranes Also its expression is modulated by cell activation state [15C17] TLR3 has been detected in a large number of tissues including the pancreas liver heart lymph nodes brain Posaconazole gastrointestinal tissue TLR expression has been shown to be particularly high in salivary glands and gingival fibroblasts [18C22] TLR3 was identified about 10 years ago as a receptor that recognizes double-stranded RNA (dsRNA).
TLR3 plays an important role in antiviral immunity and induction of adaptive immunity Its activation promotes the expression of type I interferon dsRNA molecules act as ligands of TLR3 as they are intermediates of viral replication or are part of the viral genome [23] Imatinib Polyribonosinic: polyribocytidylic acid [Poly (I:C)] is a synthetic analogue of dsRNA which has been widely used to mimic viral infections [24] Also Poly (I:C) can produce toxic effects such as shock renal failurecoagulopathies [25] and hypersensitivity reactions After recognition of dsRNA TLR3 is phosphorylated on two tyrosine residues located in the cytosolic region; this event promotes activation of signaling cascades that lead to secretion of pro-inflammatory cytokines and chemokines and to induction of transcription factors .
In macrophages Poly (I:C) promotes expression of IL-6 and activation of the JNK pathway [2728] Other research suggests that inhibition of PKC a/b causes a decrease in the purchase Irinotecan expression of IFN b induced by Poly (I:C) Furthermore Poly (I:C) activates the transcription factor AP-1 by activation of p38 and p42/44 in MDDC and mDC in blood [2930] Human gingival fibroblasts (HGFs) are the most abundant cells in the gum and participate in defense mechanisms in response to histamine which is an important mediator of allergic reactions and a wide variety of immune responses such as cytokine production and modulation of inflammatory T-helper cells HGFs express immune receptors that include TNFR CD14 and TLR [22] HGF stimulation with cytokines and lipopolysaccharide (LPS) induces the production of cytokines such as IL-1 IL-6 and IL-8 suggesting that HGFs play a very important role in inflammatory processes.
Recently it has been shown that HGF stimulation with Poly (I:C) induces the expression of pro-inflammatory molecules such as IL6 IL8 and CXCL10 [31] However an excess price Cilostazol production of these mediators can lead to the development of periodontal disease On the other hand some studies indicate that periodontitis can develop in genetically predisposed individuals who are infected with virulent agents In HGFs viral infections promote the expression of matrix metalloproteinases which leads to gum destruction [12] Fibroblasts and epithelial cells express TLR3 intracellularly as well as on pathology the surface of the cell membrane.