Research Article | Volume : 1 Issue : 5, July 2011

Epigenetic modification of suppressor of cytokine signaling-3 in asthmatic mouse lung: role of interleukin-6

Vani Mishra Rahul Sharma Brajadulal Chattopadhyay Bhola Nath Paul   

Open Access   

Abstract

Interleukin-6 (IL-6) and Suppressor of cytokine signaling-3 (Socs3) play important roles in T helper cell type 2-mediated allergic responses, and are the integral components of asthma. As IL-6 regulates the activity of DNA methyl transferases, we hypothesize that asthma is fallout of epigenetic alteration in Socs3. Here, the status of CpG methylation and histone acetylation in the Socs3 promoter of asthmatic lung was studied, as was the role of IL-6 in altering these parameters. Lung tissues from asthmatic mice were cultured in presence or absence of IL-6 and CpG methylation and histone acetylation in the functional Socs3 promoter was assessed. Functional Socs3 promoter was less methylated in asthmatic lung relative to normal lung and in vitro IL-6 treatment aberrantly altered CpG demethylation sites in asthmatic lung although the net demethylation density did not change significantly (p>0.05). 5-aza-2’- dioxycytidine induced significant CpG demethylation in normal lung but did not upregulate Ovalbumin induced-Socs3 expression. Chromatin immunoprecipitation analysis with acetylated H4 antibodies revealed a significantly (p<0.05) high enrichment of Socs3 promoter in asthmatic lung compared to normal lung. In contrast, insignificant (p>0.05) enrichment was observed in IL-6 treated asthmatic lung when compared to normal lung. Our findings implicate that asthma is associated with H4 acetylation and IL-6 causes loss of acetylated histone (H4) protein. This study provides an insight into asthma pathogenesis and delineates the role of IL-6 in epigenetic regulation of the Socs3 gene in pulmonary tissue.


Keyword:     Asthma Epigenesis Socs3 Histone acetylation IL-6.


Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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