The funders had no role in study design, Alisertib purchase data collection and analysis, decision to publish, or preparation of the manuscript.
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells, by which the injurious stimuli should be removed and the healing process initiated. Hypoxia and p38 group mitogen-activated protein kinase (p38-MAPK) have been associated with inflammatory diseases [1]�C[3]. Hypoxia inducible factor-1 (HIF-1) is the main regulator of the transcriptional response to hypoxia and its activity is modulated by the p38-MAPK signaling pathway [4], [5]. Stabilized HIF-1�� is observed in several inflamed tissues and, in the case of clinical colitis it has been detected in epithelial and inflammatory cells [6]�C[8].

In epithelial cells HIF-1 induces the expression of genes involved in mucosal defence and repair, such as mucin 3 and trefoil factors [9], [10], and has been identified as a critical factor for barrier protection. The role it plays in inflammatory cells seems to be more complex, with specific functions being reported according to the type of cell. HIF-1 increases the expression of ?2 integrin, which promotes neutrophil binding to the endothelium [11], [12], and activation of HIF has been reported during macrophage differentiation [13]. At the inflammatory focus, HIF-1 prevents the apoptosis of neutrophils and mediated bacterial phagocytosis by macrophages [12], [14]�C[16]. Considered as a whole, these observations demonstrate a protective effect of HIF-1 in epithelial cells and point to a key role in the activation of the innate immune response against pathogens and injury.

However, the involvement of HIF-1 and its transcriptional activity in the clearance of cellular debris and apoptotic cells mediated by macrophages [17], a crucial process in the resolution of inflammation, is yet to be clarified. CD36 is a heavily glycosylated transmembrane protein belonging to an evolutionarily conserved family of scavenger receptors. This multifunctional receptor is expressed on the surface of different cells, including macrophages, and is known to be involved in scavenger recognition of apoptotic cells [18], [19], exogenous pathogens and their inflammatory compounds [20].

The interaction between CD36 and apoptotic cells seems to be mediated specifically by thrombospondin-1 (TSP-1), an extracellular matrix glycoprotein that bridges apoptotic cells, CD36 and the vitronectin receptor, Anacetrapib thus creating a phagocytically active ternary complex [21]. CD36 expression is transcriptionally controlled by the nuclear receptor PPAR�� [22]. However, a recent study has demonstrated that inflammatory macrophages, in which activation of PPAR�� is down-regulated, are endowed with an alternative mechanism of CD36 expression [23].