Premium
Role of Serum Response Factor (SRF) and NFkB in Acrolein‐induced Modulation of Inflammatory Gene Expression Profiling
Author(s) -
Yousefipour Zivar,
Newaz Mohammad Ali
Publication year - 2012
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.26.1_supplement.lb648
Subject(s) - acrolein , serum response factor , gene expression , microbiology and biotechnology , chemokine , chemistry , inflammation , signal transduction , cancer research , gene , receptor , immunology , biology , biochemistry , catalysis
Inflammatory signaling in acrolein toxicity in VSMC has been proposed but signaling mediators are unknown. The issue has been further complicated by the emergence and understanding of inflammatory proteins. Previously we reported acrolein‐induced vascular toxicity requires SRF dependent activation/expression of NFkB. We confirmed that SRF inhibition attenuates NFkB. In this study we explored expression of genes involved in inflammatory process and involvement of SRF or NFkB. VSMCs were treated with acrolein (0.5 μg/ml; 24 hrs) with or without pre‐incubation with Helenalin (NFkB inhibitor; 2 μM) or CCG (SRF inhibitor; 300 nM) for 30 min. RNA was isolated, gene expression was measured using PCR array examining 84 genes. Acrolein causes over‐expression of 6 genes (4–16 fold) and under‐expression of 8 genes (7–48 fold). Casp1 (Caspase 1; 12 fold) and Cx3cl1 (Chemokine Ligand 1; 12 fold), involved in cell death and exaggerated immune response, were over‐expressed. IL11 and Spp1 were reduced 36 and 24 fold respectively. SRF inhibitor enhanced expression of Abc1, a gene responsible for ATP binding and mRNA transcription by 15 fold. SRF and NFkB inhibition reduced Cx3cl1 expression (7 fold and 4 fold respectively) that was over‐expressed in acrolein treated cells. These observations suggests that acrolein induced activation of inflammatory signaling involves expression of Cx3Cl1 gene and is SRF and NFkB dependent.