Critical role of toll-like receptor 4 (TLR4) in dextran sulfate sodium (DSS)-Induced intestinal injury and repair
| Autor: | Zhao Quanquan, Hao Wang, Xiao-Shuang Liu, Shi Yunjie, Cong Liu, Hai-Feng Gong |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Inflammation Toxicology Proinflammatory cytokine Cell Line 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans Colitis Intestinal Mucosa Mice Knockout Toll-like receptor business.industry Dextran Sulfate General Medicine medicine.disease Intestinal epithelium digestive system diseases Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal 030104 developmental biology Cytokine Immunology TLR4 lipids (amino acids peptides and proteins) Tumor necrosis factor alpha medicine.symptom business 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Toxicology letters. 315 |
| ISSN: | 1879-3169 |
| Popis: | Ulcerative colitis2 (UC) is an inflammatory bowel disease3 (IBD) that causes long-lasting inflammation and ulcers in the human digestive tract. The repair function of TLR4 in the intestinal epithelium is still unknown. Here, wild-type4 (WT) mice, TLR4-knockout mice5 (KO; TLR4-/-) and commensal-depleted mice were used as dextran sulfate sodium6 (DSS)-induced or radiation-induced colitis and injury models to explore the role of TLR4 signaling in intestinal injury. Exogenous lipopolysaccharide7 (LPS) promoted DSS-induced inflammatory cytokines and aggravated intestinal damage. TLR4 deficiency and commensal bacterial depletion inhibited the toxic effects of LPS, but these mice were more susceptible to DSS-induced and radiation-induced intestinal damage. Compared with WT mice, neither DSS nor radiation promoted production of more inflammatory cytokines in the guts of TLR4-KO and commensal-depleted mice. Introducing the cytokine repair factors, PGE2 and GM-CSF, increased the cytokine levels in the guts of DSS-induced colitis mice. We hypothesized that TLR4 and its ligands repaired the epithelium after DSS-induced and radiation-induced intestinal damage by upregulating PGE2 and GM-CSF. Transwell migration assays suggested that LPS, IL6, TNF, PGE2 and GM-CSF promoted intestinal cell migration, and cell viability analysis suggested that these factors protected against radiation-induced intestinal damage. Our data underscore the importance of the balancing role of TLR4 in intestinal injury and repair. |
| Databáze: | OpenAIRE |
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