| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The pathogenesis of fibrosing lung disease likely involves inflammatory cytokines secreted from immune effector cells. In this study RNAs were extracted from bronchoalveolar lavage fluid (BALF) cells obtained from patients with idiopathic interstitial pneumonia (IIP) (n=9), asbestosis (n=4), silicosis (n=8), lung cancer( n=6) and healthy volunteers(n=12), and mRNAs for cytokines were assessed by amplofication with reverse transcription-polymerase chain reaction(RT-PCR). The quantitative results were expressed as ratios of the amount of PCR products of cytokines and beta-actin as an internal control. The expression of TGF-beta mRNA was elevated jin the patients with IIP, asbestosis and silicosis as compared with controls of the lung cancer patients and the healthy volunteers. The expressions of IL-1beta and TNFalpha mRNA in BALF cells and IL-1beta protein titer in BALF were both suppressed in the patients with these three diseases. No significant differences were observed in the expression of IL-8 or IL-6 mRNA between the patients with lung fibrosis and the healthy volunteers. Prostaglandin E2 (PGE2) concentration in BALF from patients with lung fibrosis was higher as compared to healthy volunteers. The decreases in IL-1beta and TNFalpha production may be, in part, due to high level of PGE2 in BALF from patients. These results suggest that regulatory mechanism (s) of IL-1beta, TNFalpha and TGF-beta may be common to patients with IIP, asbestosis and silicosis, and these cytokines may significantly contribute to the alveolar damage and subseqent fibrosis. To characterriza the biololgical roles of cytokines and growth-factors in vivo, we are planning to introduce TGFbeta gene into rat lung by using HVJ-liposome.
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