| First Author | Rider P | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 9 | Pages | 4835-43 |
| PubMed ID | 21930960 | Mgi Jnum | J:179461 |
| Mgi Id | MGI:5302455 | Doi | 10.4049/jimmunol.1102048 |
| Citation | Rider P, et al. (2011) IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol 187(9):4835-43 |
| abstractText | The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells. In the current study, we assessed in a comparative manner the role of IL-1alpha and IL-1beta in the initiation and propagation of sterile inflammation induced by products of hypoxic cells. We found that following hypoxia, the precursor form of IL-1alpha, and not IL-1beta, is upregulated and subsequently released from dying cells. Using an inflammation-monitoring system consisting of Matrigel mixed with supernatants of hypoxic cells, we noted accumulation of IL-1alpha in the initial phase, which correlated with the infiltration of neutrophils, and the expression of IL-1beta correlated with later migration of macrophages. In addition, we were able to show that IL-1 molecules from cells transfected with either precursor IL-1alpha or mature IL-1beta can recruit neutrophils or macrophages, respectively. Taken together, these data suggest that IL-1alpha, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils, whereas IL-1beta promotes the recruitment and retention of macrophages. Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation. |
