Nature Medicine
- 12, 330 - 334 (2006)
Published online: 15 January 2006; | doi:10.1038/nm1355
Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependentFabiana S Machado1, James E Johndrow2, 3, Lisia Esper1, Alexandra Dias1, Andre Bafica2, 4, Charles N Serhan5 & Julio Aliberti11
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27705, USA. 2
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. 3
Fred Hutchinson Cancer Research Institute, Seattle, Washington 98109, USA. 4
Laboratorio de Imunorregulacao, Fundacao Osvaldo Cruz, Salvador, BA, Brazil 40295. 5
Center for Experimental Therapeutics, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Julio Aliberti fabiana.machado@duke.edu or Fabiana S Machado julio.aliberti@duke.edu Control of inflammation is crucial to prevent damage to the host during infection. Lipoxins and aspirin-triggered lipoxins are crucial modulators of proinflammatory responses; however, their intracellular mechanisms have not been completely elucidated. We previously showed that lipoxin A4 (LXA4) controls migration of dendritic cells (DCs) and production of interleukin (IL)-12 in vivo
1. In the absence of LXA4 biosynthetic pathways, the resulting uncontrolled inflammation during infection is lethal, despite pathogen clearance2. Here we show that lipoxins activate two receptors in DCs, AhR and LXAR, and that this activation triggers expression of suppressor of cytokine signaling (SOCS)-2. SOCS-2–deficient DCs are hyper-responsive to microbial stimuli, as well as refractory to the inhibitory actions of LXA4, but not to IL-10. Upon infection with an intracellular pathogen, SOCS-2–deficient mice had uncontrolled production of proinflammatory cytokines, decreased microbial proliferation, aberrant leukocyte infiltration and elevated mortality. We also show that SOCS-2 is a crucial intracellular mediator of the anti-inflammatory actions of aspirin-induced lipoxins in vivo.
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