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Function cytokine that presents both nuclear and extracellular functions. Extracellular IL-1 is now recognized to be an important player in sterile inflammatory diseases and cancer.117?19 IL-1 expression and intracellular function IL-1 precursor (pIL-1) is constitutively expressed in most resting nonhematopoietic cells, such as epithelial cells lining the gastrointestinal tract, liver, kidney and
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Icated in platelet activation.116 Hence, in atherosclerotic plaques, HMGB1 sensing by platelets, endothelial cells and SMCs promotes the migration and adhesion of immune cells, thereby fostering plaque formation and growth. For the past two decades, HMGB1 commanded the attention of many groups because of its central role in signaling infection and cellular damage. It has become clear that even if
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Ways (7).whereas necrotic cells can release pIL-1, resulting in myeloid cell chemotaxis and inflammation.142 In fact, the IL-1 proform is known to bind to IL-1R1 and to induce inflammation. To date, however, it is not entirely clear which of the two forms is the most relevant following cell damage. Notably, IL-1 release by stressed endothelial cells was also proposed to be mediated by the formatio
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Ways (7).whereas necrotic cells can release pIL-1, resulting in myeloid cell chemotaxis and inflammation.142 In fact, the IL-1 proform is known to bind to IL-1R1 and to induce inflammation. To date, however, it is not entirely clear which of the two forms is the most relevant following cell damage. Notably, IL-1 release by stressed endothelial cells was also proposed to be mediated by the formatio
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Otentiating its proinflammatory activity.144 Interestingly, IL-1 may also be displayed at the cell surface, where it can activate juxtaposing target cells expressing its receptor, such as T cells or endothelial cells (Figure 2).145?48 As for IL-1, once it is released into the extracellular space, soluble or membrane-bound IL-1 binds to IL-1R1 and further triggers the recruitment of the accessory r
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Released from necrotic cells and subsequently activates IL-1R1 present at the surface of mesothelial cells. This was proposed to be the prime event inducing neutrophil infiltration and peritoneal inflammation rather than the HMGB1 pathway.152,153 This proinflammatory role of IL-1 was recently confirmed in a mouse model of acute colon inflammation (dextran sodium sulfate-induced colitis), where epi
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O moderate its negative effects will be crucial for the efficient treatment of many patients. INTERLEUKIN-1a The IL-1 family of proteins contains 11 members. The beststudied family members are IL-1 and IL-1. Both are highly similar in structure and bind to the same cell membrane receptor, IL-1R. Interestingly, IL-1 receptor antagonist (IL-1Ra) is a naturally expressed member of the IL-1 family tha
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Ways (7).whereas necrotic cells can release pIL-1, resulting in myeloid cell chemotaxis and inflammation.142 In fact, the IL-1 proform is known to bind to IL-1R1 and to induce inflammation. To date, however, it is not entirely clear which of the two forms is the most relevant following cell damage. Notably, IL-1 release by stressed endothelial cells was also proposed to be mediated by the formatio