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- Title
4-1BB-mediated Signals Confer Protection Against Folic Acid-induced Nephrotoxicity.
- Authors
Li, Xiaozhong; Dai, Jihong; Qiu, Yuhua; Zhang, Xueguang
- Abstract
Background: The role of co-stimulatory molecules in renal diseases has been previously examined, however, little is known about the role of 4-1BB in the context of renal diseases resulting from nonimmune-mediated tubulointerstitial fibrosis. Folic acid induced Nephrotoxicity (FAN) in mice was used to explore the role of 4-1BB in this setting. Methods: CD1 mice were treated with folic acid and kidneys subsequently examined using histochemistry, in addition to defining T cell profiles and evaluating renal function. Increased CD3+ and CD4+ T lymphocytes present in blood and spleen at day 3 suggested immunopathological reactions during the early stages of FAN and decreased CD3+ and CD4+ T lymphocytes on day 14 were characteristic of an immunocompromised state observed during the late stages of FAN. Results: After 14 days of co-treatment with agonistic anti-4-1BB monoclonal antibodies, renal tubulointerstitial lesions were reduced. Renal function was improved, with Bun scores decreasing (p<0.01) and sCr levels decreasing (p<0.01). CD3+ and CD4+ T lymphocytes levels were increased during the early stages of disease in FA treated mice and reduced to the normal level in the 4-1BB-treated mice. CD3+ and CD4+ T lymphocytes levels were decreased in FA treated mice and returned to baseline in the 4-1BB-treated mice during later stages. Conclusions: Data presented in this report demonstrated that 4-1BB signals had immunoregulatory effects that attenuated early immune-mediated pathology and reversed the immunocompromised state observed during the later stages of disease. Copyright © 2012 S. Karger AG, Basel
- Subjects
TUBULOINTERSTITIAL nephritis &; uveitis syndrome; KIDNEY diseases; NEPHROTOXICOLOGY; FOLIC acid; HISTOCHEMISTRY
- Publication
Kidney & Blood Pressure Research, 2013, Vol 36, Issue 1, p10
- ISSN
1420-4096
- Publication type
Article
- DOI
10.1159/000339022