TY - JOUR T1 - Toll-like receptor in salivary glands from patients with Sjögren's syndrome: functional analysis by human salivary gland cell line. JF - The Journal of Rheumatology JO - J Rheumatol SP - 1019 LP - 1026 VL - 34 IS - 5 AU - Atsushi Kawakami AU - Koto Nakashima AU - Mami Tamai AU - Hideki Nakamura AU - Nozomi Iwanaga AU - Keita Fujikawa AU - Toshiyuki Aramaki AU - Kazuhiko Arima AU - Naoki Iwamoto AU - Kunihiro Ichinose AU - Makoto Kamachi AU - Hiroaki Ida AU - Tomoki Origuchi AU - Katsumi Eguchi Y1 - 2007/05/01 UR - http://www.jrheum.org/content/34/5/1019.abstract N2 - OBJECTIVE: We investigated expression of toll-like receptor (TLR) in labial salivary glands of patients with Sjögren's syndrome (SS) and functional TLR expression in the cultured salivary gland cell line. METHODS: Expression of TLR2, TLR3, TLR4, and myeloid differentiation factor 88 (MyD88) in labial salivary glands was examined by immunohistochemistry. Human salivary gland (HSG) cell-line cells were cultured with TLR ligands [peptidoglycan, poly (I:C) and lipopolysaccharide], and CD54 expression and interleukin 6 (IL-6) production was studied. Phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and Akt was examined by Western blotting. Activation of nuclear factor-kappaB (NF-kappaB) p65 in HSG cells was studied by NF-kappaB p65 nuclear translocation by microscopic immunofluorescence or chemiluminescent electrophoretic mobility shift assay and detection of NF-kappaB p65 phosphorylation. RESULTS: TLR2, TLR3, TLR4, and MyD88 were more strongly expressed in the labial salivary glands of SS patients (n =12) than in control subjects (n = 4), and were found in salivary-infiltrating mononuclear cells as well as acinar cells and ductal epithelial cells. In cultured HSG cells, a similar expression pattern was observed, and TLR ligands stimulated CD54 expression and IL-6 production. TLR ligands induced phosphorylation of ERK, JNK, and p38 in HSG cells, but not Akt phosphorylation or activation of NF-kappaB p65. CONCLUSION: Although the putative ligands remain to be determined, our study indicated the activation of the TLR-mediated immune response in SS, and suggested that the TLR effect is mediated through the mitogen-activated protein kinase pathway. ER -