INVESTIGADORES
DOCENA Guillermo Horacio
congresos y reuniones científicas
Título:
Down regulation of cytokine secretion by MAPK inhibitors in IBD
Autor/es:
DOCENA GUILLERMO H.; FANNING A; ROVEDATTI LAURA; LEAKEY NICHOLAS; KNOWLES CH; LEE K; SHANAHAN L; NALLY K; MCLEAN PG; MACDONALD THOMAS; KRUIDENIER L
Reunión:
Congreso; 6th European Mucosal Immunology Group Meeting; 2008
Resumen:
Pro-inflammatory cytokines are key pathophysiologic factors in IBD, but the
regulatory role of MAPK pathways in their expression has remained
controversial.We have evaluated the activation status of p38 and JNK MAPK
pathways and the inhibitory effect of novel p38 inhibitors. Fresh colonic
biopsies and LPMC from normal subjects and patients with CD or UC were
incubated in the presence or absence of four different p38 MAPK inhibitors
(0.0110uM). The activation status of p38α and JNK was evaluated by Western
blotting, while levels of a range of cytokines were measured by multiplex
ELISA. As compared to healthy controls, p38α and JNK phosphorylation levels, as
well as TNF-α (30500 pg/mL), IL-6 (130 ng/mL), IL-1β (201200 pg/mL) and
monocyte chemoattractant protein (MCP)-1 (3002000 pg/mL) were increased in CD
and UC biopsies. Treatment with the different inhibitory drugs down modulated
the phosphorylation of p38α and JNK MAPK, and the cytokine levels, in a
dose-dependent manner.We confirm the importance of the p38 and JNK MAPK
pathways in IBD, and identify novel p38 MAPK inhibitors which may constitute
the basis for new therapeutic strategies in IBD patients.