accumulation has been shown to be at its highest as early as 4 hours after induction of inflammation in zymosan induced peritonitis [50]. Therefore, lack of effect on neutrophil migration could be due to late time point analyzed. The data suggests that SOD3 overexpression and dexamethasone administration have similar anti-inflammatory effect in acute inflammation and therefore suggesting SOD3 as a potential candidate molecule for clinical treatments. NF-kB plays a crucial role in mediating inflammation due to its role in activating expression of pro-inflammatory genes such as cytokines TNFa and IL1a, and adhesion molecules ICAM-1 and VCAM-1 [43,44]. Since NF-kB is a redox sensitive transcription factor being activated by oxidative stress, [12,13] we analyzed the effect of SOD3 on NF-kB activity in vitro and showed significantly decreased activity. (Figure 5A). The data is in line with previous work in cardiovascular and liver transplantation models showing that increased NAPDH oxidase-derived superoxide production correlates with increased NF-kB activity, which is attenuated by SOD3 overexpression [51–54]. Since cytokines TNFa, IL1a, IL6, MIP2, and MCP1 are known to contain NF-kB binding sites in their gene promoters and are thus up-regulated by NF-kB activation [55–61], we analyzed their expression levels in rat muscle by quantitative PCR. All of the analyzed cytokines and chemokines were significantly down- regulated in SOD3 animals as compared to LacZ control animals (Figure 5B). TNFa, IL1a, and IL6 promote inflammatory cell migration by up-regulating E-selectin, P-selectin, ICAM, and VCAM. Furthermore, macrophage recruitment has been shown to be strongly dependent on MCP-1 secretion [46], while MIP2 is a strong attractant for neutrophils [35]. MCP-1 deficiency does not reduce the number of resident macrophages in peritoneal cavity, but prevents macrophage migration in response to acute thioglycollate induced peritonitis [46]. Lu et al. showed 3-fold reduction in macrophage migration in 2,4-dinitro-1-fluorobenzene induced skin hypersensitivity model while neutrophil numbers remained unchanged. Thereafter, marked down-regulation of MCP-1 seen in ischemic muscle could explain the observed strong References 1. Alom-Ruiz SP, Anilkumar N, Shah AM (2008) Reactive oxygen species and endothelial activation. Antioxid Redox Signal 10: 1089–1100. 2. Tidball JG (2005) Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 288: R345–353. 3. Rocksen D, Lilliehook B, Larsson R, Johansson T, Bucht A (2000) Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetyl- cysteine in endotoxin-induced lung inflammation. Clin Exp Immunol 122: 249–256. 4. 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(2003) VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. Am J Physiol Cell Physiol 285: C343–352. PLoS ONE | www.plosone.org 7 June 2009 | Volume 4 | Issue 6 | e5786