Journal of cellular and molecular medicine, 2020-10, Vol.24 (20), p.11936-11948
2020
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- Autor(en) / Beteiligte
- Titel
- LIGHT aggravates sepsis‐associated acute kidney injury via TLR4‐MyD88‐NF‐κB pathway
- Ist Teil von
- Journal of cellular and molecular medicine, 2020-10, Vol.24 (20), p.11936-11948
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2020
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- Sepsis‐associated acute kidney injury (SA‐AKI) is a common clinical critical care syndrome. It has received increasing attention due to its high morbidity and mortality; however, its pathophysiological mechanisms remain elusive. LIGHT, the 14th member of the tumour necrosis factor (TNF) superfamily and a bidirectional immunoregulatory molecule that regulates inflammation, plays a pivotal role in disease pathogenesis. In this study, mice with an intraperitoneal injection of LPS and HK‐2 cells challenged with LPS were employed as a model of SA‐AKI in vivo and in vitro, respectively. LIGHT deficiency notably attenuated kidney injury in pathological damage and renal function and markedly mitigated the inflammatory reaction by decreasing inflammatory mediator production and inflammatory cell infiltration in vivo. The TLR4‐Myd88‐NF‐κB signalling pathway in the kidney of LIGHT knockout mice was dramatically down‐regulated compared to the controls. Recombinant human LIGHT aggravated LPS‐treated HK‐2 cell injury by up‐regulating the expression of the TLR4‐Myd88‐NF‐κB signalling pathway and inflammation levels. TAK 242 (a selective TLR4 inhibitor) reduced this trend to some extent. In addition, blocking LIGHT with soluble receptor fusion proteins HVEM‐Fc or LTβR‐Fc in mice attenuated renal dysfunction and pathological damage in SA‐AKI. Our findings indicate that LIGHT aggravates inflammation and promotes kidney damage in LPS‐induced SA‐AKI via the TLR4‐Myd88‐NF‐κB signalling pathway, which provide potential strategies for the treatment of SA‐AKI.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1582-1838eISSN: 1582-4934DOI: 10.1111/jcmm.15815Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7579683
- Format
- –
- Schlagworte
- acute kidney injury, Acute Kidney Injury - metabolism, Acute Kidney Injury - pathology, Animals, Apoptosis, Cell injury, Cell Line, Down-Regulation, Fc receptors, Gene expression, Humans, Immunoregulation, Inflammation, Inflammation - pathology, Inflammation Mediators - metabolism, Kidneys, Laboratory animals, LIGHT, Lipopolysaccharides, Metastases, Mice, Knockout, Models, Biological, Morbidity, MyD88 protein, Myeloid Differentiation Factor 88 - metabolism, NF-kappa B - metabolism, NF‐κB, Original, Pathophysiology, Proteins, Reagents, Renal function, Sepsis, Sepsis - metabolism, Signal Transduction, Survival Analysis, TLR4, TLR4 protein, Toll-Like Receptor 4 - metabolism, Toll-like receptors, Tumor necrosis factor, Tumor Necrosis Factor Ligand Superfamily Member 14 - deficiency, Tumor Necrosis Factor Ligand Superfamily Member 14 - metabolism, Tumors