Considering that HIF-1 is significantly increased in the damaged mucosa our selleckchem Tipifarnib results propose that at sites of inflammation where the mechanisms that modulate the constitutive expression of CD36 are down-regulated, the expression of this scavenger receptor may depend on HIF-1 activity. It is important to note that both down-regulation of PPAR-�� [35] and HIF-1�� stabilization have been related to hypoxia. Taking into account that low oxygen levels are associated with inflamed tissue results lead us to suggest hypoxia as an important regulator of CD36 expression at sites of inflammation. Reinforcing this observation, both hypoxia and IBD have been related to p38-MAPK activity [4], [5], [36]�C[38] and the present study shows high expression of p38-MAPK in the damaged mucosa of IBD patients.

Positive immunostaining has been observed in epithelial cells and different cells of the lamina propria, including macrophages. Despite the high expression, the quantitative analysis of p38-MAPK immunostaining in cells of the lamina propria morphologically identified as macrophages shows a positive and significant correlation with CD36 expression. Taken together results suggest that CD36 expression at the damaged mucosa of IBD patients may depend on both p38MAPK and HIF-1 activity. It is important to note that in some samples we found a higher number of p38-MAPK positive cells than CD36 positive cells which suggests that some of the p38-MAPK positive cells are not expressing CD36. Considering that these cells have been identified as macrophages it seems likely that in the damaged mucosa of IBD patients, macrophages with a different pattern of expression may be present [39].

Further experiments are necessary to address this question. In summary, our findings reveal a mechanism by which the transcriptional Anacetrapib activity of HIF-1 coordinates induction of CD36 and TSP-1 expression in macrophages, a mechanism that mediates the enhanced phagocytosis of apoptotic neutrophils in hypoxia. In addition to its known pro-inflammatory action, HIF-1 may also constitute an important regulator in the resolution of inflammation. Supporting Information Figure S1 Hypoxia increases CD36 expression in PBMC and U937-derived macrophages. Graphs show the effect of hypoxia on the expression of CD36 in PBMC and U937-derived macrophages. Results are expressed as intensity of fluorescence in arbitrary units. Bars in the graphs represent mean�� SEM (n=3). Groups were compared using t-test analysis. Significant difference from the respective group in normoxic conditions is shown by *P<0.05. (TIF) Click here for additional data file.(819K, tif) Acknowledgments We thank Brian Normanly for English language editing.