title: Poly(I:C) induces BLyS-expression of airway fibroblasts through phosphatidylinositol 3-kinase.
abstract: B lymphocyte stimulator (BLyS), B cell activating factor (BAFF), a member of the tumor necrosis factor ligand superfamily has potent co-stimulatory activity on B cells, and BLyS-production in the airway mucosa is of potential importance as it triggers innate and adaptive immune responses. To investigate whether airway fibroblast could express BLyS, we examined BLyS-expression in human nasal airway fibroblasts and compared to its expression in tonsillar and skin fibroblasts as well as the effect of the Toll-like receptor (TLR) ligands on that in human nasal airway fibroblasts. The expression of BLyS by nasal fibroblasts in the presence of polyinocinic-polycytidykic acid (poly(I:C)) was markedly induced, to a level of more than 100 times higher than that observed in the absence of poly(I:C). In order to demonstrate the intracellular pathways involved in poly(I:C)-induced BLyS-expression, we used specific inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), spleen tyrosine kinase (Syk), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and extracellular-signal related kinase (ERK)-signaling in these events. Pre-incubation with the PI3-kinase inhibitor LY294002 or Wortmanin reversed the poly(I:C)-induced production and expression of BLyS. Syk kinase inhibitor Piceatannol partially reduced its production and expression. Thus, we were able to show that PI3-kinase signaling is directly involved in poly(I:C)-induced BLyS-expression in nasal airway fibroblasts. These results indicate that human nasal airway fibroblasts strongly induce BLyS-expression and production by poly(I:C) through PI3-K signaling during airway immune responses.
authors.affiliation: Department of Otorhinolaryngology, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, Japan. ymdtkcy@u-fukui.ac.jp
authors.forename: Takechiyo
authors.initials: T
authors.lastname: Yamada
authors.forename: Su
authors.initials: S
authors.lastname: Lizhong
authors.forename: Noboru
authors.initials: N
authors.lastname: Takahashi
authors.forename: Seita
authors.initials: S
authors.lastname: Kubo
authors.forename: Norihiko
authors.initials: N
authors.lastname: Narita
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
mesh_terms: D000328:Adult; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009666:Nose / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011070:Poly I-C / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D008024:Ligands; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011070:Poly I-C; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C505719:TNFSF13B protein, human