RGD Reference Report - Neutralization of IL-10 Exacerbates Cycloheximide-Induced Hepatocellular Apoptosis and Necrosis. - Rat Genome Database

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Neutralization of IL-10 Exacerbates Cycloheximide-Induced Hepatocellular Apoptosis and Necrosis.

Authors: Kumagai, K  Ito, K  Ando, Y  Hakamata, S  Teranishi, M  Nakayama, H  Manabe, S 
Citation: Kumagai K, etal., Toxicol Pathol. 2009 Apr 24.
RGD ID: 2306926
Pubmed: PMID:19395591   (View Abstract at PubMed)
DOI: DOI:10.1177/0192623309336153   (Journal Full-text)

Cycloheximide (CHX)-induced liver injury in rats has been characterized by hepatocellular apoptosis and necrosis. We previously reported that Kupffer cell inactivation causes a reduction of IL-10 production, resulting in the exacerbation of CHX-induced liver injury. In this study, we directly evaluate the role of IL-10 in liver injury by a pretreatment with anti-IL-10 neutralizing antibody (IL-10Ab). Rats were given goat IgG or IL-10Ab before being treated with CHX (CHX group or IL-10Ab/CHX group). In the CHX group, the CHX treatment markedly induced hepatic mRNA and serum protein levels of IL-10. The up-regulation of IL-10 was significantly suppressed in the IL-10Ab/CHX group. Blocking IL-10 in the IL-10Ab/CHX group led to greater increases in hepatic mRNA and serum levels of proinflammatory cytokines, such as TNF-alpha and IL-6. The IL-10Ab/CHX group developed more severe hepatocellular apoptosis, neutrophil transmigration, and necrotic change of hepatocytes compared with the CHX group. The caspase activities and mRNA levels of Cc120, LOX-1, and E-selectin in the livers were significantly higher in the IL-10Ab/CHX group than the CHX group. These results demonstrate that IL-10 plays an important role in counteracting the effect of proinflammatory cytokines, such as a TNF signaling cascade, and in attenuating the CHX-induced liver injury.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 2306926 RGD 
response to cytokine  IEP 2306926Il-10 inhibitionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)
Il6  (interleukin 6)


Additional Information