P026 Effect of Toll-like receptor-2 deficiency on transcriptomic profile in DSS-colitis

2012 
fibrosis (p = 0.004 and 0.00004), those receiving PC/TNBS had significantly less inflammation (p = 0.009), while those treated with PC/Indo/TNBS had less inflammation and fibrosis (p = 0.001 and 0.03). At 6 weeks compared to TNBS alone, inflammation and fibrosis was not different in the Indo/TNBS and PC/Indo/TNBS-treated animals, but PC/TNBS-treated animals had less inflammation (p = 0.01) and fibrosis (p = 0.006). The addition of PC to Indo/TNBS at 2 weeks significantly decreased inflammation and fibrosis compared to Indo/TNBS alone (p = 0.03 and 0.00001), however at 6 weeks, this addition had no effect on Indo/TNBS-induced inflammation or fibrosis. In CCD-18co cells the addition of DLPC increased MMP-1 and TIMP-1 mRNA expression (p = 0.03 and 0.01), with no effect on Col1 or TGF-b1 suggesting that DLPC may decrease ECM deposition. By contrast, LPPC increased Col1 (p = 0.0008) and TIMP-1 (p = 0.03) and decreased MMP-1 expression (p = 0.003) with no effect on TGF-b1 suggesting that LPPC may increase ECM deposition. DLPC/Indo and LPPC/Indo treatment mirrored DLPC and LPPC treatment alone. Conclusions: The findings demonstrate that PC can reduce inflammation and fibrosis but may require a higher dose to completely abolish the effects of Indo/TNBS in vivo. The PC isoform appears to be important in vitro as DLPC may decrease and LPPC increase ECM deposition by isolated fibroblasts.
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