| First Author | Sekiyama A | Year | 2005 |
| Journal | Immunity | Volume | 22 |
| Issue | 6 | Pages | 669-77 |
| PubMed ID | 15963782 | Mgi Jnum | J:99113 |
| Mgi Id | MGI:3581121 | Doi | 10.1016/j.immuni.2005.04.006 |
| Citation | Sekiyama A, et al. (2005) A Stress-Induced, Superoxide-Mediated Caspase-1 Activation Pathway Causes Plasma IL-18 Upregulation. Immunity 22(6):669-677 |
| abstractText | Psychological/physical stresses are known to cause relapses of autoimmune and inflammatory diseases. To reveal a mechanism by which noninflammatory stresses affect host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via adrenocorticotropic hormone (ACTH) and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form, which was released into plasma. Inhibitors of caspase-1, reactive oxygen species, and P38 mitogen-activated protein kinase (MAPK) suppressed stress-induced accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6 expression. This, together with the observation that IL-6 was not induced in IL-18-deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In stressed organisms, IL-18 may influence pathological and physiological processes. Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide preventative means against stress-related disruption of host defenses. |
