CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Salmonella dam mutant induces low NOS-2 and COX-2 expression via MAPK and NF-kB pathways attenuation in macrophages.
Autor/es:
M. CRISTINA CERQUETTI, EUGENIA HOVSEPIAN, SEBASTIAN H. SARNACKI AND NORA B. GOREN.
Revista:
MICROBES AND INFECTION
Editorial:
Elsevier Science
Referencias:
Lugar: Amsterdam; Año: 2008 vol. 10 p. 1431 - 1439
ISSN:
1286-4579
Resumen:
Although dam mutants of Salmonella have been proposed as live vaccines,
their capacity to trigger cell inflammatory cascades has not been fully
elucidated. We investigated in detail the ability of Salmonella
enterica dam mutant to activate the signalling pathways of the
inflammatory response in RAW 264.7 cells. Apoptosis in macrophages
treated with Salmonella dam mutant was low. Similarly, the expression
of both NOS-2 and COX-2 and subsequently the production of NO and
PGE(2) was significantly reduced. Also, Salmonella dam mutant induced
an attenuated activation of the inflammatory signalling pathway as
indicated by the reduced degradation of IkappaBalpha and IkappaBbeta
and the low IkappaBalpha phosphorylation found. In addition,
translocation of p65 to the nucleus was notably impaired and the amount
of phosphorylated p44, p42 and p38 MAPKs was clearly reduced in
extracts from dam-infected macrophages. These results indicate that the
lack of ERK and p38 phosphorylation at the proper time in dam-infected
cells notably reduces the engagement of subsequent signalling pathways
involved in the full activation of NF-kappaB in response to infection.
Taken together, these results suggest that Salmonella activation of
both signalling cascades in the inflammatory response is a mechanism
requiring Dam protein participation.