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

Zhang, Ping ; Chen, Ying LU ; Zhang, Tao ; Zhu, Jiang ; Zhao, Lei ; Li, Jianshuang ; Wang, Guangzhi ; Li, Yongchun ; Xu, Shuchang and Nilsson, Åke LU , et al. (2018) In Journal of Lipid Research 59(10). p.1841-1850
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
interleukin 10, interleukin 6, lysophosphatidic acid, nucleotide pyrophosphatase phosphodiesterase 2, nucleotide pyrophosphatase phosphodiesterase 7, platelet activating factor, sphingomyelinase, tumor necrosis factor α
in
Journal of Lipid Research
volume
59
issue
10
pages
10 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:30087205
  • scopus:85054060867
ISSN
1539-7262
DOI
10.1194/jlr.M084285
language
English
LU publication?
yes
id
531430b4-a18f-42fc-aa18-389cc062aaec
date added to LUP
2018-10-09 13:20:53
date last changed
2025-04-04 14:11:52
@article{531430b4-a18f-42fc-aa18-389cc062aaec,
  abstract     = {{<p>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.</p>}},
  author       = {{Zhang, Ping and Chen, Ying and Zhang, Tao and Zhu, Jiang and Zhao, Lei and Li, Jianshuang and Wang, Guangzhi and Li, Yongchun and Xu, Shuchang and Nilsson, Åke and Duan, Rui Dong}},
  issn         = {{1539-7262}},
  keywords     = {{interleukin 10; interleukin 6; lysophosphatidic acid; nucleotide pyrophosphatase phosphodiesterase 2; nucleotide pyrophosphatase phosphodiesterase 7; platelet activating factor; sphingomyelinase; tumor necrosis factor α}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1841--1850}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Lipid Research}},
  title        = {{Deficiency of alkaline SMase enhances dextran sulfate sodium-induced colitis in mice with upregulation of autotaxin}},
  url          = {{http://dx.doi.org/10.1194/jlr.M084285}},
  doi          = {{10.1194/jlr.M084285}},
  volume       = {{59}},
  year         = {{2018}},
}