Journal
JOURNAL OF LIPID RESEARCH
Volume 59, Issue 10, Pages 1841-1850Publisher
ELSEVIER
DOI: 10.1194/jlr.M084285
Keywords
lysophosphatidic acid; nucleotide pyrophosphatase phosphodiesterase 2; nucleotide pyrophosphatase phosphodiesterase 7; platelet activating factor; interleukin 10; interleukin 6; tumor necrosis factor alpha; sphingomyelinase
Categories
Funding
- National Natural Science Foundation of China [81500407]
- 57th General Financial Postdoctoral Science Foundation in China [2015M571435]
- Heilongjiang Postdoctoral Science Foundation in China [LBH-Z15144]
- Cancerfonden in Sweden
- Albert Pahlsson Foundation in Sweden
- Crafoord Foundation in Sweden
- Region Skane University Hospital Foundation in Sweden
Ask authors/readers for more resources
Intestinal alkaline SMase (Alk-SMase) cleaves phosphocholine from SM, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4- to 5-fold enhanced in Alk-SMase KO mice. Here, we further studied the pathogenesis of colitis induced by dextran sulfate sodium (DSS) in WT and KO mice. Compared with WT mice, KO mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury. Higher levels of PAF and lower levels of interleukin (IL)10 were identified in KO mice 2 days after DSS treatment. A greater and progressive increase of lysophosphatidic acid (LPA) was identified. The change was associated with increased autotaxin expression in both small intestine and colon, which was identified by immunohistochemistry study, Western blot, and sandwich ELISA. The upregulation of autotaxin coincided with an early increase of PAF. IL6 and TNF alpha were increased in both WT and KO mice. At the later stage (day 8), significant decreases in IL6, IL10, and PAF were identified, and the decreases were greater in KO mice. In conclusion, deficiency of Alk-SMase enhances DSS-induced colitis by mechanisms related to increased autotaxin expression and LPA formation. The early increase of PAF might be a trigger for such reactions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available