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1.
Br J Pharmacol ; 179(23): 5209-5221, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35906855

RESUMO

BACKGROUND AND PURPOSE: The constitutive androstane receptor (CAR), a known xenobiotic sensor, plays an important role in drug metabolism by regulating numerous genes. The polycyclic aromatic hydrocarbon pyrene, an environmental pollutant, is a CAR activator and induces mouse hepatotoxicity via CAR. Here, we investigate the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury. EXPERIMENTAL APPROACH: Effects of pyrene on the liver were investigated in wild-type and CAR knockout (KO) mice. Levels of pyrene and its urinary metabolite were analysed by high performance liquid chromatography (HPLC). Inflammatory responses were measured by qRT-PCR, western blotting, and ELISA for cytokines. KEY RESULTS: Serum amyloid A proteins (SAAs) were markedly increased in the liver and serum of pyrene-exposed wild-type mice. IL-17-producing helper T cells (Th17 cells) and IL-17 levels were increased in the liver of pyrene-exposed wild-type mice. Hepatic mRNA levels of inflammatory cytokines including IL-1ß, IL-6 and TNFα, and serum IL-6 levels were significantly elevated in pyrene-treated wild-type mice. However, these changes were not observed in CAR KO mice. CONCLUSION AND IMPLICATIONS: CAR plays a crucial role in pyrene-caused mice liver inflammatory response with increased SAAs and Th17 cells. Our results suggest that serum SAAs may be a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene. CAR and Th17 cells may be potential targets for novel therapeutic strategies for xenobiotic-induced liver inflammation.


Assuntos
Receptor Constitutivo de Androstano , Pirenos , Animais , Camundongos , Receptor Constitutivo de Androstano/metabolismo , Interleucina-17 , Interleucina-6 , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pirenos/toxicidade , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteína Amiloide A Sérica/metabolismo , Células Th17 , Xenobióticos/toxicidade
2.
Artigo em Chinês | MEDLINE | ID: mdl-21351557

RESUMO

The full-length pBluescript II SK cDNA library of adult Spirometra erinaceieuropaei was constructed by using the SMART method. Data showed that 95.5% of the library was recombinant and the titer of the library was 1.06 x 10(6). The average insert size of the library was about 1.4 kb. Forty-eight randomly selected clones were sequenced. A set of 36 effective expressed sequence tags (ESTs) with the average size of 674 bp was obtained after excluding clones shorter than 450 bp. The unigenes occupied 58.3% of the 36 ESTs. The rate of full-length cDNAs were 57.7% (15/26). The high-quality of full-length cDNA library could be used for large scale EST sequencing.


Assuntos
DNA Complementar/genética , Biblioteca Gênica , Spirometra/genética , Animais , Sequência de Bases
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