Deficiency of alkaline SMase enhances dextran sulfate sodium-induced colitis in mice with upregulation of autotaxin

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 TNFα 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.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Gastroenterologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Gastroenterology and Hepatology hsv//eng
interleukin 10
interleukin 6
lysophosphatidic acid
nucleotide pyrophosphatase phosphodiesterase 2
nucleotide pyrophosphatase phosphodiesterase 7
platelet activating factor
sphingomyelinase
tumor necrosis factor α

Chen, YingLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Tongji University,Tongji Medical University(Swepub:lu)med-ycn (författare)
Zhang, TaoHarbin Medical University (författare)
Zhu, JiangHarbin Medical University (författare)
Zhao, LeiHarbin Medical University (författare)
Li, JianshuangHarbin Medical University (författare)
Wang, GuangzhiHarbin Medical University (författare)
Li, YongchunHarbin Medical University (författare)
Xu, ShuchangTongji University,Tongji Medical University (författare)
Nilsson, ÅkeLund University,Lunds universitet,Gastro,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-ani (författare)
Duan, Rui DongLund University,Lunds universitet,Gastro,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-rdd (författare)
Harbin Medical UniversityMedicin, Lund (creator_code:org_t)

Av författaren/redakt...: Zhang, Ping; Chen, Ying; Zhang, Tao; Zhu, Jiang; Zhao, Lei; Li, Jianshuang; visa fler...; Wang, Guangzhi; Li, Yongchun; Xu, Shuchang; Nilsson, Åke; Duan, Rui Dong; visa färre...

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