Open AccessExpression of IL ‐33 and its epigenetic regulation in multiple sclerosis
Author(s) -
Zhang Fanglin,
Tossberg John T.,
Spurlock Charles F.,
Yao SongYi,
Aune Thomas M.,
Sriram Subramaniam
Publication year - 2014
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.47
Subject(s) - trichostatin a , epigenetics , innate immune system , histone deacetylase , gene expression , lipopolysaccharide , immune system , immunology , histone , medicine , gene , inflammation , regulation of gene expression , microbiology and biotechnology , biology , genetics
Objective We examined the expression of IL‐33 as an indicator of an innate immune response in relapsing remitting MS (RRMS) and controls. We proposed a link between the expression of IL‐33 and IL‐33 regulated genes to histone deacetylase (HDAC) activity and in particular HDAC3, an enzyme that plays a role in the epigenetic regulation of a number genes including those which regulate inflammation. Methods Using TaqMan low density arrays, flow cytometry and ELIZA, expression of IL‐33, and family of innate immune response genes which regulate cytokine gene expression was examined in RRMS patients and controls. Results Intracellular expression of IL‐33 and IL‐33 regulated genes are increased in patients with RRMS. In addition, following in vitro culture with TLR agonist lipopolysaccharide (LPS), there is increased induction of both IL‐33 and HDAC3 in RRMS patients over that seen in controls. Also, culture of PBMC with IL‐33 led to the expression of genes which overlapped with that seen in RRMS patients suggesting that the gene expression signature seen in RRMS is likely to be driven by IL‐33 mediated innate immune pathways. Expression of levels of IL‐33 but not IL‐1 (another gene regulated by TLR agonists) is completely inhibited by Trichostatin A (TSA) establishing a closer regulation of IL‐33 but not IL‐1 with HDAC. Interpretation These results demonstrate the over expression of innate immune genes in RRMS and offer a causal link between the epigenetic regulation by HDAC and the induction of IL‐33.