285 HYPOXIA – INDUCED MIGRATION OF HEPATIC STELLATE CELLS AND BONE MARROW – DERIVED MESENCHYMAL STEM CELLS INVOLVES COMMON REDOX MECHANISMS

April 23 weeks (TAA-PFD group).Hepatic biopsies were taken after PFD therapy in control (Non TAA), fibrotic (TAA) and TAA-PFD groups.Fibrosis was measured by morphometric analysis.Necro-inflammatory index was evaluated by the Modified histological activity index (HAI) of Knodell.Gene expression of IL-4 (Th2 cytokine), IFN-g (Th1 cytokine), T-bet, GATA3 (Th1 and Th2 transcriptional factors respectively), a1 (I) col, TNF-a, IL-6 and TGF-b1 were analyzed by real time RT-PCR.Western blots were performed from liver homogenates to evaluate phosphorylated p38 MAPK, CXCR3 and CCR4 proteins (Th1 and Th2 chemokine receptors, respectively), Th transcriptional factors and Th cytokines.Results: Transcripts for a1 (I) col, GATA3 and IL-4, as well as CCR4 protein and inflammatory infiltration were found increased in TAA group.PFD therapy induced down-regulation of both Th2 transcripts and proteins; IL-4 and GATA3, and diminished TNF-a and a1 (I) col mRNAs.Interestingly, PFD reduced significantly p38 activation, which coincides whit the anti Th2 effect observed with PFD administration.No changes were observed in IL-6, T-bet and IFN-g transcripts or in CXCR3 and CCR4 proteins with PFD treatment.Inflammation evaluated by HAI and liver fibrosis measured by morphometric analysis was dramatically reduced in PFD treated rats.Conclusions: TAA-induced liver fibrosis is characterized by a Th2 response.PFD is capable of limiting Th2 profibrogenic cytokines gene expression in this Th2 polarized environment via p38 inhibition.Additionally, our results confirmed the anti-inflammatory and anti-fibrotic activities of PFD.