ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis.
The authors have investigated gene expression of ST2 in the lung tissue of a bleomycin (BLM)-induced lung fibrosis model in vivo and in a human lung fibroblast cell line, WI38, and a human type II alveolar epithelial cell line, A549, reacting to proinflammatory and type 2 helper T cell (Th2)-type cytokine stimuli in vitro. The lung mRNA expression of interleukin (IL)-4, IL-5, IL-1beta, and tumor necrosis factor (TNF)-alpha increased significantly at day 7 after instillation of BLM, whereas interferon (IFN)-gamma mRNA expression did not increase. ST2 and transforming growth factor (TGF)-beta1 mRNA expression of the lung increased significantly between days 7 and 21, and increased to maximal levels at day 14 post-BLM challenge. ST2 mRNA expression statistically correlated with TGF-beta 1 mRNA expression. In addition, the combination of IL-1 beta, TNF-alpha, and IL-4 had an additive effect on ST2 mRNA expression from A549 cells and WI38 cells. These findings suggest that soluble ST2 gene may increase, possibly reflecting the development of the inflammatory process and the Th2-type immune response in the fibrotic lung tissue, and may modulate a process of pulmonary fibrosis.
Tajima
Shunji
S
Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan. tajimash@med.niigata-u.ac.jp
Bando
Masashi
M
Ohno
Shoji
S
Sugiyama
Yukihiko
Y
Oshikawa
Katsuhisa
K
Tominaga
Shin-ichi
S
Itoh
Kouichi
K
Takada
Toshinori
T
Suzuki
Eiichi
E
Gejyo
Fumitake
F
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004338:Drug Combinations; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
D016207:Cytokines; D004338:Drug Combinations; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D006909:Hydroxyproline