M1803 Differential Degradation of Anti-Tumor Necrosis Factor-α Agents by Matrix Metalloproteinase-12 in Inflammatory Bowel Disease
Gastroenterology(2010)
摘要
with active ileal inflammation, autophagy was nearly absent.Those patients were also non responders to anti-TNFs.By contrast, in patients without inflammation who had responded to anti-TNFs, LC3+ cells were frequently seen and were more common than UC controls.To understand the consequence of autophagy on TNF production, we asked whether autophagy changed the response of RAW cells (macrophage cell line) to lipopolysaccharide (LPS).We induced autophagy in RAW cells using rapamycin and confirmed their viability by trypan blue staining.RAW cells stimulated with rapamycin had increased expression of LC3-II as determined by western blot.Cells were then stimulated with LPS, after induction of autophagy, and TNFα levels were measured.We found that cells undergoing autophagy had decreased production of TNFα (974.6 ± 65.7 pg/ml) compared with the cells stimulated with LPS but not treated with rapamycin (1,409.6 ± 115.5 pg/ml; p=0.006).CONCLUSIONS: These results suggest that autophagy is present in patients with CD in remission from anti-TNF therapy.The process of autophagy itself may be important to dampen pro-inflammatory cytokine secretion in response to bacterial products such as LPS.
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关键词
tumor necrosis factor,matrix metalloproteinase
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