期刊
MOLECULAR IMMUNOLOGY
卷 133, 期 -, 页码 146-153出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2021.02.024
关键词
Hemodialysis; Axl; Growth arrest 6; Inflammation
资金
- National Natural Science Foundation of China [81571574, 81570628, 81971822]
- Incubation Program for National Natural Science Foundation of China [04.03.19.101]
This study found that inflammatory cytokines, sAxl, and Gas6 levels were significantly increased in HD patients, with sAxl positively correlated with IL-6. mAxl in CD14(+) mononuclear cells and CD19(+) B cells was elevated in HD patients. Furthermore, the metalloproteinase ADAM17 contributed to the cleavage of mAxl into sAxl.
Background: Hemodialysis (HD) patients often develop chronic inflammation, which is associated with an increased risk of cardiovascular complications and mortality. Axl and its ligand, growth arrest 6 (Gas6), have been reported to play key roles in regulating the immune response. However, the function of Axl in HD patients has not been clarified. Methods: In the present study, we enrolled 130 HD patients and 117 normal controls (NCs) and evaluated the levels of inflammatory markers, soluble Axl (sAxl), membrane Axl (mAxl), and Gas6 in all participants. The potential downstream cascades of Gas6-Axl signaling in HD patients were identified by quantitative real time polymerase chain reaction and western blotting. Results: The levels of inflammatory cytokines-tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)-plasma sAxl, and Gas6, were significantly increased in HD patients compared to NCs. Additionally, sAxl was positively associated with the inflammatory factor, interleukin-6 (IL-6), in HD patients. Moreover, we found that mAxl in CD14(+) mononuclear cells and CD19(+) B cells was increased upon HD. Furthermore, we discovered that the metalloproteinase ADAM17, also called TACE, contributed to the cleavage of mAxl into sAxl, and not ADAM10, in the peripheral blood mononuclear cells (PBMCs) of HD patients. The upregulation of Gas6-mAxl signaling caused the activation of the STAT1-SOCS3 pathway in the PBMCs of HD patients. After two years follow-up, patients with lower sAxl levels had longer survival time than those with higher sAxl levels. Conclusion: Our results suggest that Axl may play a significant role in systemic inflammation in HD patients.
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