Li_2013_Environ.Toxicol_28_349

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-kappaB (NF-kappaB), NF-kappaBp52, NF-kappaBp65, NF-kappaB-inducing kinase (NIK), IkappaB kinase alpha (IKK-alpha), IkappaB kinase beta (IKK-beta), and tumor necrosis factor-alpha (TNF-alpha) expression, and suppress NF-kappaB-inhibiting factor (IkappaB) 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-alpha-->NIK-->IkappaB kinase (including IKK1, IKK2)-->NF-kappaB (including NF-kappaBP52, NF-kappaBP65)--> inflammation. (c) 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.