title: Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl₃.
abstract: To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl₃, we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl₃ decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-κB (NF-κB), NF-κBp52, NF-κBp65, NF-κB-inducing kinase (NIK), IκB kinase α (IKK-α), IκB kinase β (IKK-β), and tumor necrosis factor-α (TNF-α) expression, and suppress NF-κB-inhibiting factor (IκB) and interleukin-2 (IL-2) expression in liver. Taken together, the inflammation of mice liver caused by exposure to CeCl₃ might be closely associated with the alteration of inflammatory cytokine expressions in the mouse liver, the signal-transducing events happening in CeCl₃-induced macrophages of liver sequentially might occur via activation of TLRs→TNF-α→NIK→IκB kinase (including IKK1, IKK2)→NF-κB (including NF-κBP52, NF-κBP65)→ inflammation.
authors.affiliation: Medical College, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cai
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
authors.forename: Yaling
authors.initials: Y
authors.lastname: Cui
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D002563:Cerium / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007075:Immunoglobulin M / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D051193:Toll-Like Receptors; D002563:Cerium; D000410:Alanine Transaminase; C026690:cerous chloride