RESUMO
The 5'-upsteam region of the genomic gene and cDNA encoding interleukin 4 (IL-4) has been isolated and sequenced from the inbred mouse strain MSKR derived from a Japanese wild mouse using polymerase chain reaction (PCR) methodology. The cDNA sequence of IL-4 of MSKR was found to contain several nucleotide alterations, which result in amino acid substitutions, in comparison with that of inbred mouse BALB/c. In MSKR, IL-4 was expressed at high levels in thymus and spleen as revealed by reverse transcriptase PCR method and Northern hybridization. The tissue-specific expression profile was quite similar to that of laboratory mice.
Assuntos
DNA Complementar/metabolismo , Regulação da Expressão Gênica , Interleucina-4/genética , Animais , Animais Endogâmicos , Sequência de Bases , Clonagem Molecular , Interleucina-4/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Homologia de Sequência do Ácido Nucleico , Timo/citologia , Distribuição TecidualRESUMO
BACKGROUND: Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice. METHODS: NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4). RESULTS: Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions. CONCLUSION: Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.
