Although the physiologi cal role of this process is not well understood, it is likely that CCR2 down regulation may be involved in restricting the reverse migration of differentiated monocytes back into the blood stream. This in turn facilitates the retention of differentiated monocytes within inhibitor price inflamed tissues. Thus, by improving our understanding of the regulatory mecha nisms that govern CCR2 e pression on monocyte lineage cells, we can better appreciate how monocyte recruitment and activation is controlled during chronic inflammatory pathologies such as atherosclerosis. Background Elevated levels of plasma homocysteine are associated with chronic kidney disease and end stage renal disease irrespective of the underlying aetiol ogy.

However, the pathophysiological consequences of hyperhomocysteinemia remain controversial because, although Hhcy has consistently been associated with morbidity and mortality, recent epidemiologic stud ies have produced conflicting results. In a prospective community based study of persons without kidney dis ease at study inception, over a 5 year period, chronic kid ney disease risk was found to increase in association with escalating Hcy levels in both men and women. The converse has been also reported. that is, chronic kidney disease is a direct cause of Hhcy. Hcy levels rises in direct relationship to reduction in glomerular filtration rates. Given the e istence of these inconsistent observations, the role of Hcy in progressive kidney disease is unresolved and continues to be the focus of ongoing clinical and basic investigations.

Notwithstanding contradictory observations, studies have identified an association between Hcy and inflammation. For instance, in subject aged 65 years, IL 6 and IL 1ra cytokines were independent predictors of plasmatic Hcy concentrations. Similarly, in another study, serum Hcy levels and C reactive protein levels were significantly higher in patients with stage 3 chronic kidney disease compared to those with stage 1 disorder. In this regard, the potential consequences of Hhcy on inflamma tion in the kidney have been studied by assessing the impact of Hcy on monocyte chemoattractant protein 1 e pression by glomerular mesangial cells. Hcy induced MCP 1 protein and mRNA levels in glomerular MC via nuclear factor kappa B activation, a process found to be mediated by generation of o idative stress.

In a related study, the same investigators observed that in methionine induced Hhcy rats, MCP 1 protein and mRNA levels were increased in kidneys Brefeldin_A and that this increase was dependent on NF ?B. The authors surmised that these observations link Hcy induced inflammatory response to kidney injury and progressive kidney disease. We have demonstrated that Hcy induces DNA damage and apoptosis in MC. These adverse effects were depend ent on Hcy induced o idative stress and p38 MAPK activa tion.