ST2 GENE INDUCED BY TYPE 2 HELPER T CELL (TH2) AND PROINFLAMMATORY CYTOKINE STIMULI MAY MODULATE LUNG INJURY AND FIBROSIS

Author: Tajima Shunji   Bando Masashi   Ohno Shoji   Sugiyama Yukihiko   Oshikawa Katsuhisa   Tominaga Shin-ichi   Itoh Kouichi   Takada Toshinori   Suzuki Eiichi   Gejyo Fumitake  

Publisher: Informa Healthcare

ISSN: 1521-0499

Source: Experimental Lung Research, Vol.33, Iss.2, 2007-03, pp. : 81-97

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Abstract

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-1β, and tumor necrosis factor (TNF)-α increased significantly at day 7 after instillation of BLM, whereas interferon (IFN)-γ mRNA expression did not increase. ST2 and transforming growth factor (TGF)-β1 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-β 1 mRNA expression. In addition, the combination of IL-1 β, TNF-α, 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.

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