31 research outputs found
Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63
Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity
PHLEBOTOMINE FAUNA (DIPTERA: PSYCHODIDAE) IN AN AREA OF FISHING TOURISM IN CENTRAL-WESTERN BRAZIL
Rotating Stars in Relativity
Rotating relativistic stars have been studied extensively in recent years,
both theoretically and observationally, because of the information one could
obtain about the equation of state of matter at extremely high densities and
because they are considered to be promising sources of gravitational waves. The
latest theoretical understanding of rotating stars in relativity is reviewed in
this updated article. The sections on the equilibrium properties and on the
nonaxisymmetric instabilities in f-modes and r-modes have been updated and
several new sections have been added on analytic solutions for the exterior
spacetime, rotating stars in LMXBs, rotating strange stars, and on rotating
stars in numerical relativity.Comment: 101 pages, 18 figures. The full online-readable version of this
article, including several animations, will be published in Living Reviews in
Relativity at http://www.livingreviews.org