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PMID: 17082634 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 177 ·No. 10 ·2006-11-15 ·Pages 7164-72

Kato A, Truong-Tran AQ, Scott AL, Matsumoto K, Schleimer RP

Abstract

Activation of B cells in the airways is now believed to be of great importance in immunity to pathogens, and it participates in the pathogenesis of airway diseases. However, little is known about the mechanisms of local activation of B cells in airway mucosa. We investigated the expression of members of the B cell-activating TNF superfamily (B cell-activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL)) in resting and TLR ligand-treated BEAS-2B cells and primary human bronchial epithelial cells (PBEC). In unstimulated cells, expression of BAFF and APRIL was minimal. However, BAFF mRNA was significantly up-regulated by TLR3 ligand (dsRNA), but not by other TLR ligands, in both BEAS-2B cells (376-fold) and PBEC (224-fold). APRIL mRNA was up-regulated by dsRNA in PBEC (7-fold), but not in BEAS-2B cells. Membrane-bound BAFF protein was detectable after stimulation with dsRNA. Soluble BAFF protein was also induced by dsRNA (> 200 pg/ml). The biological activity of the epithelial cell-produced BAFF was verified using a B cell survival assay. BAFF was also strongly induced by IFN-beta, a cytokine induced by dsRNA. Induction of BAFF by dsRNA was dependent upon protein synthesis and IFN-alphabeta receptor-JAK-STAT signaling, as indicated by studies with cycloheximide, the JAK inhibitor I, and small interfering RNA against STAT1 and IFN-alphabeta receptor 2. These results suggest that BAFF is induced by dsRNA in airway epithelial cells and that the response results via an autocrine pathway involving IFN-beta. The production of BAFF and APRIL by epithelial cells may contribute to local accumulation, activation, class switch recombination, and Ig synthesis by B cells in the airways.

MeSH Terms
B-Cell Activating Factor/biosynthesis Bronchi/cytology,immunology,metabolism CD40 Ligand/biosynthesis Cell Line, Transformed Cells, Cultured Cytokines/physiology Epithelial Cells/immunology,metabolism Glucocorticoids/pharmacology Humans Interferon-beta/physiology Ligands RNA, Double-Stranded/pharmacology Respiratory Mucosa/cytology,immunology,metabolism Toll-Like Receptor 3/metabolism Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis Tumor Necrosis Factors/biosynthesis
Chemicals
B-Cell Activating Factor Cytokines Glucocorticoids Ligands RNA, Double-Stranded Toll-Like Receptor 3 Tumor Necrosis Factor Ligand Superfamily Member 13 Tumor Necrosis Factors CD40 Ligand Interferon-beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kato Atsushi
Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Truong-Tran Ai Q
Scott Alan L
Matsumoto Kenji
Schleimer Robert P
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
DOI
10.4049/jimmunol.177.10.7164
Published
2006-11-15
Pages
7164-72
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2804942
Subset
IM
Grants
NHLBI NIH HHS · R01 HL068546 · United States
NHLBI NIH HHS · R01 HL068546-22 · United States
NHLBI NIH HHS · R01 HL078860 · United States
NHLBI NIH HHS · R01 HL078860-01A1 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.177.10.7164 PMC Full Text View journal details
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