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Epigenetic regulation of LPS‐induced lung injury by sphingosine‐1‐phosphate lyase (1001.10)
Author(s) -
Ebenezer David,
Zhao Yutong,
Ackerman Steven,
Natarajan Viswanathan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1001.10
Subject(s) - histone deacetylase , acetylation , chemistry , sphingosine 1 phosphate , lipopolysaccharide , epigenetics , sphingosine , histone , inflammation , microbiology and biotechnology , biochemistry , biology , immunology , receptor , gene
Sphingosine‐1‐Phosphate Lyase (SGPL1) irreversibly hydrolyses Sphingosine‐1‐Phosphate (S1P) to ethanolamine phosphate and hexadecenal in mammalian cells. We have earlier demonstrated that inhibition or down‐regulation of Sphingose‐1‐Phosphate Lyase (SGPL1) ameliorates lipopolysaccharide (LPS)‐induced lung inflammation in mice. Therefore, challenge causes lung injury by increasing Sphingosine‐1‐Phosphate Lyase (SGPL1) expression, and inhibition of SGPL1 activity could produce therapeutic levels of immunosuppression. Our study is aimed to define SGPL1 mediated epigenetic regulation of LPS‐induced inflammatory responses in lung endothelium. Our preliminary data showed that down regulation of S1PL with siRNA blocked LPS‐induced IL‐6 secretion and partially blocked LPS‐induced acetylation of Histone H3 and Histone H4. Also, knock down of SGPL1 decreased MYST2 and IL‐6 promoter activity and potentiated Histone Deacetylase (HDAC) 5 expression. Moreover, Blocking HDAC activity with Trischostatin A potentiated LPS‐induced IL‐6 secretion while Histone Acetyl transferase (HAT) inhibitor Anacardic acid attenuated IL‐6 production. Taken together, these data reveal a potential epigenetic regulation mediated by SGPL1 in LPS‐induced lung inflammation. Grant Funding Source : Supported by National Institute of health P01HL098050