extent as proteins, but whether PE modification is required for the inflammatory actions of lipid aldehydes is unknown. We found that PE modified by lipid aldehydes (al-PEs), particularly PE modified by γ-ketoaldehydes (γKA-PE) could stimulate THP-1 monocyte adhesion to human umbilical vein endothelial cell (HUVEC). Treatment of HUVEC by γKA-PE induced expression of ER stress signals in HUVEC and monocyte adhesion could be significantly reduced by chemical inhibitors of ER stress. To characterize the full spectrum of al-PEs that form during lipid peroxidation, we oxidized liposomes containing dipalmitoyl PE and measured the resulting al-PEs by precursor scanning mass spectrometry. We identified at least 10 major species of al-PE in addition to γKA-PE. When we measured these same al-PEs in high density lipoprotein (HDL) exposed to myeloperoxidase, we found γKA-PEs to be the most abundant al-PE formed. We then evaluated potential strategies to mitigate the proinflammatory effects of γKA-PE. Salicylamine, a potent scavenger of γKAs, blocked HUVEC activation induced by γKA. L-4F, an ApoAI mimetic peptide, bound γKA-PE with extremely high affinity (Kd 4.7 pM) and inhibited HUVEC activation by γKA-PE , while a scrambled peptide did not. We also found that NAPE-PLD, a highly unusual phospholipase D that hydrolyzes N-acyl-PE but not PE, could rapidly hydrolyze γKA-PE to γKA-ethanolamine, which is only a weak activator of HUVEC. Thus, γKA-PE and other al- PEs are potent inflammatory mediators whose contribution to inflammatory disease associated with lipid peroxidation can be tested by use of selective interventional strategies. doi:10.1016/j.freeradbiomed.2011.10.369 246 Polymorphism in the TNF-alpha Gene Promoter is Associated With Increased Circulating Levels of TNF- alpha, Myeloperoxidase and Nitrotyrosine in Primary Sjogren’s Syndrome Serdar Dogan 1 , Fatih Cay 2 , Ilhan Sezer 2 , Rasih Felek 3 , and Mutay Aslan 1 1 Department of Biochemistry, Akdeniz University, 2 Physical Medicine-Rheumatology Clinic, Antalya Research and Education Hospital, Antalya, Turkey., 3 Clinical Microbiology, Akdeniz University Medical School. Objective: Tumor necrosis factor (TNF)-alpha is a pro- inflammatory cytokine which is associated with the pathogenesis of many inflammatory diseases. the aim of this study was to investigate the effect of TNF-alpha (-1031) gene polymorphism on circulating TNF-alpha, myeloperoxidase (MPO) and nitrotyrosine (NT) levels in primary Sjogren’s syndrome patients. Materials and Methods: TNF-alpha -1031 T/C gene polymorphism was evaluated in 65 Sjogren’s syndrome patients and 58 age and gender matched controls via real time PCR-single nucleotide polymorphism analysis. Plasma TNF-alpha and NT levels were analyzed by ELISA while MPO activity, total nitrate/nitrite and glutathione (GSH) levels were measured by spectral analysis. Results: TNF-alpha -1031 C carrier genotype frequency was significantly higher (p=0.045) in Sjogren’s patients compared to controls (23.1 vs. 10.3%, 0R= 2.83, 95% CI=0.27-7.8). Plasma TNF-alpha concentration and NT levels were also significantly higher in Sjogren’s patients with -1031 C carrier genotype compared to patients with TT genotype. Sjogren’s patients showed a significant increase in plasma MPO activity which correlated with both TNF alpha and NT levels in subjects with - 1031 C carrier genotype assessed by linear regression analysis. TNF-alpha -1031 T/C gene polymorphism had no effect on plasma nitrate/nitrite and GSH levels which were significantly decreased in Sjogren’s syndrome patients compared to controls. Conclusions: Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha which is correlated with increased plasma MPO activity and protein nitration in Sjogren’s Syndrome. doi:10.1016/j.freeradbiomed.2011.10.370 247 Thioredoxin Overexpression in Cell Nuclei Potentiates Atherosclerosis Via Activation of NF-κB Transcription Factor Young-Mi Go 1 , Dong Ju Son 1 , Heonyong Park 2 , Dong Won Kang 1 , Chan Woo Kim 1 , Michael Orr 1 , Hanjoong Jo 1 , and Dean P Jones 1 1 Emory University, 2 Dankook University Oxidative stress, a contributing factor to chronic inflammatory diseases, including cardiovascular disease (CVD), causes oxidation of biological thiols. Thioredoxin (Trx) is the major cellular antioxidant controlling thiol/disulfide redox state of numerous proteins including transcription factors. Cell culture studies show that the Trx1 translocates to cell nuclei during stress, facilitates DNA binding of transcription factors NF-κB and glucocorticoid receptor and potentiates signaling in the immune system. Accumulating data show that compartmentalized redox signaling controlled by the Trx1 system is critical for cell physiology and pathophysiology. in addition, our previous study showed that expression of Trx1 in cell nuclei stimulated H1N1 influenza virus- induced inflammatory signaling in the lung and immune cells, which resulted in increased mortality. This finding led us to hypothesize that nuclear Trx1 stimulates atherosclerosis development via NF-κB-activated inflammatory signaling mechanism. for the current study, we have developed transgenic mice (Tg) expressing human Trx1 with added nuclear localization signal (NLS) or with nuclear exporting signal (NES). Results show that NLS-Trx1 Tg mice exposed to disturbed blood flow stimulated increase in carotid wall thickness, foam cell formation, and expression and activation of p65 NF-κB with no significant difference in levels of lipids and weight gain when compared with WT. in contrast, NES-Trx1 Tg mice do not show significant difference in carotid wall thickness compared to that of WT. Decreased plasma glutathione and oxidized plasma glutathione redox potential in NLS-Trx1 Tg mice showed that the increased nuclear thiol antioxidant caused a paradoxical downstream oxidative stress. These results suggest that nuclear Trx1 mediates proinflammatory signaling and disease severity by potentiation of redox-sensitive transcription factor activation. the results suggest that compartmentalized thiol/disulfide redox state- based pharmacologic interventions may be effective in preventing inflammatory diseases or progression. doi:10.1016/j.freeradbiomed.2011.10.371 248 Mitochondrial ROS Induce NLRP3 S- Glutathionylation in SAA-Stimulated Macrophages Joshua Jabaut 1 , Jennifer L Ather 2 , Matthew E Poynter 2 , and Karina Ckless 1 1 SUNY Plattsburgh, 2 University of Vermont NLRP3 is a cysteine-rich protein that is a component of the “NLRP3 inflammasome”, a multiprotein complex that mediates caspase1-dependent processing and secretion of IL-1β and IL-18. Several reports implicate mitochondria-derived reactive oxygen species (ROS) as necessary for the initial steps of NLRP3 inflammasome activation. Upon changes in cellular ROS status, redox sensitive proteins are susceptible to oxidative post- translational modification, such as S-gluathionylation. Previously, SFRBM 2011 S104