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Leukocyte‐derived Myeloperoxidase modulates the expression of multiple Hepatic Gene Families during acute systemic Inflammation
Author(s) -
Vasu Vihas T,
Hemmad Aseem R,
Kubala Lukas,
Rathnayake Samira,
Gohil Kishorchandra,
Cross Carroll E,
Eiserich Jason P
Publication year - 2008
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.22.1_supplement.798.10
Subject(s) - myeloperoxidase , gene , inflammation , gene expression , microarray analysis techniques , microbiology and biotechnology , biology , s100a9 , microarray , downregulation and upregulation , chemistry , immunology , biochemistry
Myeloperoxidase (MPO) is a hemoprotein/enzyme abundantly expressed by leukocytes [neutrophils, macrophages, kupfer cells (liver)] that catalyzes the formation of free radical species implicated in inflammatory processes. The capacity of MPO to modulate gene expression during inflammatory events remains incompletely characterized. We have compared global hepatic gene expression profiles in male wild‐type (MPO+/+) and MPO‐deficient (MPO−/−) mice subjected to endotoxemia. Male mice were euthanized 24 hrs following i.p. injection of either sterile saline or E. coli LPS (10 mg/kg), liver tissue harvested, mRNA extracted and subjected to microarray analysis using Affymetrix 430 2.0 GeneChips. Global gene expression analysis demonstrated that the number of differentially expressed genes in LPS treated MPO−/− mice were dramatically higher (3156 genes) than MPO+/+ mice (1519 genes). The data showed a LPS‐induced upregulation of genes related to inflammatory‐immune responses in both MPO+/+ and MPO−/− mice. Genes related to metabolic processes were downregulated in both MPO+/+ and MPO−/− mice treated with LPS, where the effect was more in MPO−/− mice (342 genes) as compared to MPO+/+ mice (128 genes). The present data suggest that inflammatory and metabolic processes are co‐ordinately dysregulated in LPS‐challenged MPO−/− mice and provide documentation of novel genes which might be regulated by MPO.