| First Author | Daryadel A | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 10 | Pages | 6527-32 |
| PubMed ID | 19414807 | Mgi Jnum | J:148316 |
| Mgi Id | MGI:3844358 | Doi | 10.4049/jimmunol.0803846 |
| Citation | Daryadel A, et al. (2009) RhoH/TTF negatively regulates leukotriene production in neutrophils. J Immunol 182(10):6527-32 |
| abstractText | Leukotriene B(4) (LTB(4)) is an important proinflammatory lipid mediator generated by neutrophils upon activation. GM-CSF stimulation is known to enhance agonist-mediated LTB(4) production of neutrophils within minutes, a process called 'priming'. In this study, we demonstrate that GM-CSF also limits the production of LTB(4) by neutrophils via a transcriptional mechanism at later time points. We identified hemopoietic-specific Ras homologous (RhoH)/translocation three four (TTF), which was induced following GM-CSF stimulation in neutrophils, as a key regulator in this process. Neutrophils derived from RhoH/TTF-deficient (Rhoh(-/-)) mice demonstrated increased LTB(4) production upon activation compared with normal mouse neutrophils. Moreover, neutrophils from cystic fibrosis patients expressed enhanced levels of RhoH/TTF and generated less LTB(4) upon activation compared with normal human neutrophils. Taken together, these data suggest that RhoH/TTF represents an inducible feedback inhibitor in neutrophils that is involved in the limitation of innate immune responses. |
