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Salmonella Typhimurium induces HXA3 secretion by decreasing cellular levels and activity of the oxido‐reductase enzymes GPX 1 and PHGPX
Author(s) -
AGBOR Terence,
McCormick Beth
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.276.1
Subject(s) - secretion , glutathione peroxidase , chemistry , salmonella , enzyme , peroxidase , biochemistry , intracellular , lipoxygenase , microbiology and biotechnology , glutathione , biology , bacteria , genetics
Salmonella Typhimurium ( S. Typhimurium)‐induced transepithelial migration of neutrophils rapidly follows attachment of the bacteria to the epithelial apical membrane. We have previously reported that hepoxilin A 3 (HXA 3 ) mediates the final step in this process. HXA 3 is a derivative of arachidonic acid formed from the enzymatic action of the 12‐lipoxygenase (12‐LOX) pathway. However, the molecular mechanisms regulating the activity/expression of 12‐LOX during S . Typhimurium‐induced intestinal inflammation remains unknown. Thus, we sought to decipher the mechanisms regulating 12‐LOX and increased HXA 3 secretion during S . Typhimurium infection. We found that the protein expressions of Glutathione peroxidase (GPX) 1 and PHGPX (GPX 4), known to have an inhibitory effect on 12‐LOX activity, are significantly decreased during S . Typhimurium infection as well as an ~20% decrease in total cellular GPX activity. We also show that inhibition of total cellular GPX activity by iodoacatetate treatment, which increases 12‐LOX activity, resulted in a significant increase in neutrophil transmigration during S. Typhimurium infection. These results suggest that S . Typhimurium induces apical secretion of HXA 3 by decreasing the expression of cellular GPX, which in turn leads to an increase in 12‐LOX activity. We are currently performing RNAi studies to determine which GPX isoform is responsible for these functions.