RhoH/TTF negatively regulates leukotriene production in neutrophils

Daryadel, Arezoo; Yousefi, Shida; Troi, David; Schmid, Inès; Schmidt-Mende, Jan; Mordasini, Carlo; Dahinden, Clemens A; Ziemiecki, Andrew; Simon, Hans-Uwe (2009). RhoH/TTF negatively regulates leukotriene production in neutrophils. Journal of immunology, 182(10), pp. 6527-32. Bethesda, Md.: American Association of Immunologists 10.4049/jimmunol.0803846

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Yousefi, Shida; Dahinden, Clemens A. and Simon, Hans-Uwe

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.4049/jimmunol.0803846

PubMed ID:

19414807

Web of Science ID:

000265899800072

URI:

https://boris.unibe.ch/id/eprint/30710 (FactScience: 194988)

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