Current opinion in immunology
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Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by epigenetic changes. Transcriptional co-activators possess intrinsic histone acetyltransferase (HAT) activity, and histone acetylation plays a major role in inflammatory gene expression. Other marks such as histone methylation are also associated with gene induction and gene repression. ⋯ This effect of HDAC inhibitors may be due to their effects on cell death acting through acetylation of non-histone proteins. The role of epigenetic modifications in inflammatory gene expression and in the control of cell function in the airways is becoming clearer. Targeting specific enzymes involved in this process may lead to new therapeutic agents, in particular, in situations where current anti-inflammatory therapies are currently suboptimal.
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The extent of airway remodeling correlates with severity of asthma. Persistent airway hyperresponsiveness (AHR) is associated with airway remodeling, but not with inflammation. The increase in ASM mass is recognized as one of the most important factors related to AHR and to the severity of asthma. ⋯ The mediators such as tryptase and cytokines from MCs can modulate ASM cell function and induce goblet cell hyperplasia. MCs were found to contribute to the development of multiple features of chronic asthma in MC-deficient mice. Therefore, MCs play an important role not only in immediate hypersensitivity and late phase inflammation but also in tissue remodeling in the airway.