ArticleJournal of inflammation (London, England)2009
Inhibition of zymosan-induced kidney dysfunction by tyrphostin AG-490.
Article in Journal of inflammation (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Hidden attributes of zymosan in the pathogenesis of inflammatory diseases: A tale of the fungal agent.Iranian journal of basic medical sciences · 2023Review
- IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis.Nature communications · 2022Article
- Activation of α7 Nicotinic Acetylcholine Receptor Ameliorates Zymosan-Induced Acute Kidney Injury in BALB/c Mice.Scientific reports · 2018Article
- Tyrosine kinase inhibitor tyrphostin AG490 retards chronic joint inflammation in mice.Inflammation · 2014Article
- The transcriptional activation of the cyclooxygenase-2 gene in zymosan-activated macrophages is dependent on NF-kappa B, C/EBP, AP-1, and CRE sites.Inflammation · 2011Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundZymosan-induced shock has been associated with an increased production of pro-inflammatory cytokines and mediators, causing a generalized dysfunction of liver, lung and kidneys. Herein, we investigate the effects of tyrphostin AG-490 on the early inflammation and on the late renal injury provoked by zymosan injection.
methodsShock was induced by intraperitoneal injection of zymosan in a dose of 0.8-1.0 mg/g body weight in BALB/c mice and 0.8 mg/g body weight in SCID mice. Tyrphostin AG-490 was administered intraperitoneally in a dose of 5 mg/kg immediately after shock induction. Blood, peritoneal lavage and kidneys were collected at certain time points after zymosan injection. The levels of MIP-1alpha, RANTES, IL-6, IL-10, alpha1-antitrypsin and C5a in plasma were determined by ELISA. The number of IL-10-secreting cells in peritoneum was assayed by ELISPOT. Kidney function was monitored by measurement of urine/plasma creatinine levels and proteinuria. Histological assessment of renal injury was performed in a blinded fashion after hematoxylin/eosin staining. Immunohistochemistry analyses were used to evaluate the expression of C5aR, STAT1, STAT3 and the binding ability of IgGs in kidneys.
resultsTyrphostin AG-490 attenuated the early phase of zymosan-induced shock via inhibition of MIP-1alpha, RANTES and C5a plasma levels and via elevation of IL-10 in plasma. The drug increased IL-10 production in peritoneum and the number of IL-10-secreting peritoneal cells. AG-490 was able to retain the time of coagulation and the level of alpha1-antitrypsin to normal values. At the late stage of shock, AG-490 decreased scores of tubular injury, cell infiltration and glomerular lesions in parallel with diminished creatinine plasma level and protein excretion. These beneficial effects of AG-490 were related to lowered levels of circulating IL-6, MIP-1alpha and C5a, and to inhibited expression of STAT1, STAT3 and C5aR in kidneys. The drug diminished the production of zymosan-specific IgG antibodies and hindered the glomeruli from IgGs recognition.
conclusionTyrphostin AG-490 reduced the magnitude of the initial inflammatory response in zymosan-induced shock and prevented the development of severe kidney dysfunction. Our data suggest that the drug might be used as a therapeutic approach in cases where shock is combined with acute renal injury.
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Registered trials
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