title: Toll-like receptor (TLR) expression and TLR‑mediated interleukin-8 production by human submandibular gland epithelial cells.
abstract: Toll-like receptor (TLR) family members are pattern recognition receptors that are essential in the activation of innate and adaptive immune responses. Submandibular gland epithelial cells (SMGCs) may recognize microbial components through TLRs and be involved in the development of inflammatory reactions in the submandibular glands. Therefore, the functional expression of TLRs in SMGCs was investigated in the present study. The mRNA expression of TLRs in SMGC and whole submandibular tissues was determined by RT-PCR. Subsequently, the effects of various TLR agonists and tumor necrosis factor alpha (TNF-α) on IL-8 production were examined using an ELISA. SMGCs, as well as whole submandibular tissues, expressed TLR1-10 mRNA. Furthermore, interleukin (IL)-8 production in SMGCs was increased by Pam3CSK4 (TLR1/2 agonist), poly I:C (TLR3 agonist), E. coli lipopolysaccharide (LPS; TLR4 agonist), flagellin (TLR5 agonist) and macrophage‑activating lipopeptide (MALP)-2 (TLR2/6 agonist) treatments in a dose‑dependent manner, whereas administration of either imiquimod (TLR7 agonist) or CpG-oligodeoxynucletide (TLR9 agonist) exerted no evident effect. Pam3CSK4, poly I:C, LPS, flagellin and MALP-2 also enhanced TNF‑α‑induced IL-8 production in SMGCs. These findings suggest that innate immune responses against microbial components result in the development of TNF-α-mediated autoimmune inflammatory disease in the submandibular glands.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Fukui
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mizuta
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nishi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takechi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kamata
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D061251:Primary Cell Culture; D013363:Submandibular Gland / Q000166:cytology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; C439524:TNF protein, human; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha