| First Author | Luheshi NM | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 3 | Pages | 716-25 |
| PubMed ID | 22105559 | Mgi Jnum | J:187797 |
| Mgi Id | MGI:5438199 | Doi | 10.1002/eji.201142079 |
| Citation | Luheshi NM, et al. (2012) Sphingosine regulates the NLRP3-inflammasome and IL-1beta release from macrophages. Eur J Immunol 42(3):716-25 |
| abstractText | Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that regulates inflammatory responses to injury and infection. IL-1beta secretion requires the protease caspase-1, which is activated following recruitment to inflammasomes. Endogenous danger-associated molecular patterns (DAMPs) released from necrotic cells activate caspase-1 through an NLRP3-inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1beta from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited Sph-induced IL-1beta release. IL-1beta release induced by other well-characterized NLRP3-inflammasome activators, such as ATP and uric acid crystals, in addition to NLRC4 and AIM2 inflammasome activators was also blocked by these inhibitors. Thus, we propose Sph as a new DAMP, and that a serine/threonine phosphatase (PP1/PP2A)-dependent signal is central to the endogenous host mechanism through which diverse stimuli regulate inflammasome activation. |
