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CFTR mutation/downregulation induces inflammation in mouse small intestine (902.1)
Author(s) -
Liu Kaisheng,
Zhang Xiaohu,
Chan Hsiao Chang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.902.1
Subject(s) - downregulation and upregulation , inflammation , cystic fibrosis , cystic fibrosis transmembrane conductance regulator , transfection , mutation , biology , cancer research , immunology , microbiology and biotechnology , gene , genetics
Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians which is caused by the mutations of CFTR (cystic fibrosis transmembrane regulator) gene. CF presents a multitude of clinical manifestations with chronic inflammation in the lung as one of the hallmarks. In our study, we also found increased inflammation in the small intestine of CFTR DF508 mutation mice. The length of the small intestine, the thickness of the smooth muscle layer and the depth of the crypt were all increased significantly in DF508 mutants. The NF‐κB signaling pathway was found activated with the upregulation of p105/50 and increased nuclear translocation of p65. COX‐2 expression was increased significantly, which is a key player of inflammation. Further more, downregulation of CFTR in intestinal cell line Caco‐2 cells by transfection of CFTR siRNA also induced increased inflammation markers including TNFα, IL6, IL8 and IL18. Meanwhile, the mRNA of COX‐2 increased 124.84±4.26%. Both in vivo and in vitro results indicate that defect in CFTR may directly link to the activation of inflammatory pathways, such as NF‐κB and COX‐2, which may promote abnormal growth of the small intestine.