| First Author | Khameneh HJ | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 7 | Pages | e23025 |
| PubMed ID | 21829580 | Mgi Jnum | J:175831 |
| Mgi Id | MGI:5287514 | Doi | 10.1371/journal.pone.0023025 |
| Citation | Khameneh HJ, et al. (2011) GM-CSF signalling boosts dramatically IL-1 production. PLoS One 6(7):e23025 |
| abstractText | GM-CSF is mostly known for its capacity to promote bone marrow progenitor differentiation, to mobilize and mature myeloid cells as well as to enhance host immune responses. However the molecular actions of GM-CSF are still poorly characterized. Here we describe a new surprising facet of this 'old' growth factor as a key regulator involved in IL-1beta secretion. We found that IL-1beta release, a pivotal component of the triggered innate system, is heavily dependent on the signaling induced by GM-CSF in such an extent that in its absence IL-1beta is only weakly secreted. GM-CSF synergizes with LPS for IL-1beta secretion mainly at the level of pro-IL-1beta production via strengthening the NF-kappaB signaling. In addition, we show that expression of Rab39a, a GTPase required for caspase-1 dependent IL-1beta secretion is greatly augmented by LPS and GM-CSF co-stimulation suggesting a potential GM-CSF contribution in enhancing IL-1beta exocytosis. The role of GM-CSF in regulating IL-1beta secretion is extended also in vivo, since GM-CSF R-/- mice are more resistant to LPS-mediated septic shock. These results identify GM-CSF as a key regulator of IL-1beta production and indicate GM-CSF as a previously underestimated target for therapeutic intervention. |
