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Abstract: PO2042

Indoxyl Sulfate Reduces the Inducibility of NLRP3 Inflammasome in Hemodialysis Patients

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Ho, Li-chun, I-Shou University, School of Medicine, Kaohsiung City, Taiwan
  • Min-Yu, Chang, E-Da Hospital, Division of Nephrology, Department of Internal Medicine, Yanchao, Kaohsiung, Taiwan
  • Lee, Yi-che, E-Da Hospital, Division of Nephrology, Department of Internal Medicine, Yanchao, Kaohsiung, Taiwan
  • Wang, Hsi-Hao, E-Da Hospital, Division of Nephrology, Department of Internal Medicine, Yanchao, Kaohsiung, Taiwan
  • Wu, Ching-fang, E-Da Hospital, Division of Nephrology, Department of Internal Medicine, Yanchao, Kaohsiung, Taiwan
  • Hung, Shih-Yuan, E-Da Hospital, Division of Nephrology, Department of Internal Medicine, Yanchao, Kaohsiung, Taiwan
Background

The NLRP3 inflammasome is a cellular component of innate immunity responsible for the maturation of interleukin-1β (IL-1β). Studies have shown that the basal activity of the NLRP3 inflammasome is increased in the immune cells of hemodialysis (HD) patients, but the inducibility of the NLRP3 inflammasome upon canonical stimulation has not been studied.

Methods

Peripheral blood mononuclear cells (PBMCs) isolated from 13 HD patients and 18 volunteers without a history of chronic kidney disease (CKD) were treated with a combination of lipopolysaccharide (LPS) and nigericin to induce NLRP3 inflammasome activation. Likewise, THP-1 monocytic cell-derived macrophages, with or without indoxyl sulfate (IS) pretreatment, underwent the canonical NLRP3 inflammasome stimulus as well. The activity of the inflammasome was determined by immunoblot analysis.

Results

Despite the high plasma levels of IL-1β in HD patients, caspase-1 and IL-1β in the PBMCs of HD patients remained predominantly immature and were not secreted in response to the canonical stimulus. Further investigations showed that while IS treatment alone facilitated the secretion of IL-1β from THP-1-derived macrophages, IS pretreatment reduced the inducibility of NLRP3 inflammaosme in response to LPS and nigericin, characterized by the low mature rate of caspase-1. The PBMCs derived from the HD patients and the macrophages exposed to IS both had low expression levels of NLRP3 inflammasome components, suggesting insufficient supplies of inflammasome machinery.

Conclusion

The low stimulation response of the NLRP3 inflammasome attributed to indoxyl sulfate probably constitutes a breach of the immune defense system, which may explain the high infection risk in HD patients.

Funding

  • Clinical Revenue Support