| First Author | Gross O | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 3 | Pages | 388-400 |
| PubMed ID | 22444631 | Mgi Jnum | J:187333 |
| Mgi Id | MGI:5436205 | Doi | 10.1016/j.immuni.2012.01.018 |
| Citation | Gross O, et al. (2012) Inflammasome activators induce interleukin-1alpha secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36(3):388-400 |
| abstractText | Through their capacity to sense danger signals and to generate active interleukin-1beta (IL-1beta), inflammasomes occupy a central role in the inflammatory response. In contrast to IL-1beta, little is known about how IL-1alpha is regulated. We found that all inflammasome activators also induced the secretion of IL-1alpha, leading to the cosecretion of both IL-1 cytokines. Depending on the type of inflammasome activator, release of IL-1alpha was inflammasome dependent or independent. Calcium influx induced by the opening of cation channels was sufficient for the inflammasome-independent IL-1alpha secretion. In both cases, IL-1alpha was released primarily in a processed form, resulting from intracellular cleavage by calpain-like proteases. Inflammasome-caspase-1-dependent release of IL-1alpha and IL-1beta was independent of caspase-1 catalytic activity, defining a mode of action for caspase-1. Because inflammasomes contribute to the pathology of numerous chronic inflammatory diseases such as gout and diabetes, IL-1alpha antagonists may be beneficial in the treatment of these disorders. |
