Interferon lambda modulates proinflammatory cytokines production in PBMCs from patients with chronic kidney disease.


Journal

Human immunology
ISSN: 1879-1166
Titre abrégé: Hum Immunol
Pays: United States
ID NLM: 8010936

Informations de publication

Date de publication:
Sep 2023
Historique:
received: 27 12 2022
revised: 06 06 2023
accepted: 06 06 2023
medline: 14 8 2023
pubmed: 3 7 2023
entrez: 2 7 2023
Statut: ppublish

Résumé

CKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFNλ plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFNλ with CKD is still poorly understood. To analyze the correlation between IFNλ levels and pro-inflammatory cytokines, and to investigate the effect of IFNλ on PBMCs in patients with CKD. PBMCs were harvested from patients with CKD and healthy controls for measuring the expression level of inflammatory cytokines by RT-qPCR. Spearman correlation test was used to analyze correlation between IFNλ and cytokines as well as eGFR. PBMCs from healthy individuals and CKD patients were subjected to IFNλ protein stimulation. IL6, TNFα, IL10, ISG15 and MX1 mRNA level were measured by RT-PCR, STAT1 and phosphorylated STAT1 protein level were measured by Western blot. Patients with CKD showed higher levels of IFNλ in PBMCs compared to healthy controls. IFNλ mRNA levels were associated with cytokines and eGFR. The transcription of IL6, TNFα, and IL10 was significantly increased in healthy human PBMCs after IFNλ stimulation. In addition, IFNλ acts on PBMCs by p-STAT1 and ISG15 as well as MX1. High expression of IFNλ was found in CKD patients and was associated with eGFR and disease-related cytokines. More importantly, IFNλ promoted the expression of pro-inflammatory cytokines in PBMCs, suggesting a potential pro-inflammatory role of IFNλ in CKD.

Sections du résumé

BACKGROUND BACKGROUND
CKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFNλ plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFNλ with CKD is still poorly understood.
OBJECTIVE OBJECTIVE
To analyze the correlation between IFNλ levels and pro-inflammatory cytokines, and to investigate the effect of IFNλ on PBMCs in patients with CKD.
METHODS METHODS
PBMCs were harvested from patients with CKD and healthy controls for measuring the expression level of inflammatory cytokines by RT-qPCR. Spearman correlation test was used to analyze correlation between IFNλ and cytokines as well as eGFR. PBMCs from healthy individuals and CKD patients were subjected to IFNλ protein stimulation. IL6, TNFα, IL10, ISG15 and MX1 mRNA level were measured by RT-PCR, STAT1 and phosphorylated STAT1 protein level were measured by Western blot.
RESULTS RESULTS
Patients with CKD showed higher levels of IFNλ in PBMCs compared to healthy controls. IFNλ mRNA levels were associated with cytokines and eGFR. The transcription of IL6, TNFα, and IL10 was significantly increased in healthy human PBMCs after IFNλ stimulation. In addition, IFNλ acts on PBMCs by p-STAT1 and ISG15 as well as MX1.
CONCLUSION CONCLUSIONS
High expression of IFNλ was found in CKD patients and was associated with eGFR and disease-related cytokines. More importantly, IFNλ promoted the expression of pro-inflammatory cytokines in PBMCs, suggesting a potential pro-inflammatory role of IFNλ in CKD.

Identifiants

pubmed: 37394297
pii: S0198-8859(23)00085-X
doi: 10.1016/j.humimm.2023.06.001
pii:
doi:

Substances chimiques

Tumor Necrosis Factor-alpha 0
Interferon Lambda 0
Interleukin-10 130068-27-8
Interleukin-6 0
Cytokines 0
RNA, Messenger 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

464-470

Informations de copyright

Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Yuhao Xia (Y)

Weifang Medical University, Shandong, China; Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: 767277519@qq.com.

Qiannan Yang (Q)

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: 461405445@qq.com.

Shang Ying Wu (SY)

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: wu_shangying@163.com.

Zhicheng Wu (Z)

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: 13823598545@163.com.

Qian Li (Q)

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: 1239326951@qq.com.

Jing Du (J)

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: dujing83@pkuszh.com.

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Classifications MeSH