Waverunner
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https://www.sciencedaily.com/releases/2020/09/200929173415.htm
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In the new study, the authors show tofacitinib can reverse gut leakiness in mice caused by loss of PTPN2 activity. Until now, the effects of tofacitinib on intestinal barrier function in an animal model were largely unknown.
McCole explained that increased intestinal permeability -- or leakiness -- is a feature of inflammatory bowel disease and plays a critical role in promoting inflammation. His team also tested tofacitinib in a system where PTPN2 expression was reduced in human intestinal epithelial cell lines and macrophages that were then cultured together to study the effects on epithelial permeability. The team also studied mice that had increased gut leakiness resulting from the removal of PTPN2 only in macrophages. The researchers found tofacitinib repaired inflammation-induced permeability defects in both the cell culture system and in mice.
"Patients with the loss-of-function mutations in PTPN2 have an increased risk of inflammatory bowel disease," McCole said. "Our work improves our understanding of how this drug is useful for treating ulcerative colitis and suggests that patients with loss-of-function mutations in the PTPN2 gene may have a better response to tofacitinib. This could help with improved targeting of drug treatments to specific groups of patients."
...
In the new study, the authors show tofacitinib can reverse gut leakiness in mice caused by loss of PTPN2 activity. Until now, the effects of tofacitinib on intestinal barrier function in an animal model were largely unknown.
McCole explained that increased intestinal permeability -- or leakiness -- is a feature of inflammatory bowel disease and plays a critical role in promoting inflammation. His team also tested tofacitinib in a system where PTPN2 expression was reduced in human intestinal epithelial cell lines and macrophages that were then cultured together to study the effects on epithelial permeability. The team also studied mice that had increased gut leakiness resulting from the removal of PTPN2 only in macrophages. The researchers found tofacitinib repaired inflammation-induced permeability defects in both the cell culture system and in mice.
"Patients with the loss-of-function mutations in PTPN2 have an increased risk of inflammatory bowel disease," McCole said. "Our work improves our understanding of how this drug is useful for treating ulcerative colitis and suggests that patients with loss-of-function mutations in the PTPN2 gene may have a better response to tofacitinib. This could help with improved targeting of drug treatments to specific groups of patients."