Mechanism of tissue injury, repair and regeneration in inflammation, and regulation of remodeling

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Our findings in this project are as follows : 1. We prepared active recombinant protein of eosinophil granule protein, eosinophil associated ribonuclease (Ear)-1 and Ear-2. 2. The fraction of eosinophil granule protein showed no activity to induce epithelial cell injury. 3. Histone deacetylase (HDAC) inhibitor, apicidine and n-butyrate, induced eosinophil differentiation. 4. TPA and TNF-α induced the expression of ICAM-1 in human epithelial cell line NCI-H292 via the activation of NF-κB. In addition, the TPA-induce activation of NF-κB and expression of ICAM-1 were negatively regulated by p44/42 MAP kinase. 5. BEAS-2B cells, a human epithelial cell line, expressed E-cadherin as a result from the differentiation and morphological changes. 6. Histamine did not affect the proliferation and differentiation of epithelial cells although histamine enhanced angiogenesis via inducing VEGF production. These results suggested that eosinophil granule protein alone does not induce tissue injury. The activation of epithelial cells might be enhanced the cytotoxicity of eosinophils. In addition, histamine does not promote the repair and regeneration of epithelial tissues although histamine enhances fibrosis. Thus, histamine might promote remodeling of epithelial tissues.