Histone Deacetylases Affect Transcriptional Regulation of CCL2 and CXCL8 Expression by Pulmonary Fibroblasts In Vitro

Introduction: Chemokines have been shown to play an important role in tissue remodeling and fibrosis in the respiratory system. In this study we wanted to evaluate the mechanisms, which regulate the expression of selected chemokines by pulmonary fibroblasts in vitro. Material and methods: Pulmonary fibroblasts were cultured with and without bacterial lipopolysaccharide (LPS) for 6 hours. In addition some of the cultures were pre-treated with histone deacetylase inhibitor Trichostatin A (TSA). Real-time PCR reaction was performed to estimate the expression of chemokines CCL2, CCL3 and CXCL8. Results: In unstimulated cultures detectable expression of CCL2 and CXCL8 was observed, while CCL3 expression could not be detected. After stimulation with LPS, TSA and both agents together CCL2 expression rose by 1.52, 1.62 and 1.8 times in comparison to control cultures respectively. CXCL8 mRNA expression levels after stimulation with LPS, TSA and LPSTSA increased by 1.53, 1.91 and 2.4 times accordingly. Conclusion: Epigenetic mechanisms related to histone acetylation affects transcriptional regulation of CCL2 and CXCL8 expression by pulmonary fibroblasts. Those mechanisms may play a role in tissue repair and pathologic remodeling.