1. IL-1beta genotype-related effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells under acute inflammation.
- Author
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Markova S, Nakamura T, Makimoto H, Ichijima T, Yamamori M, Kuwahara A, Iwaki K, Nishiguchi K, Okamura N, Okumura K, and Sakaeda T
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Acute Disease, Adult, Alleles, Cells, Cultured, Data Interpretation, Statistical, Female, Genotype, Haplotypes, Humans, In Vitro Techniques, Lipopolysaccharides pharmacology, Male, RNA, Messenger biosynthesis, Anti-Inflammatory Agents pharmacology, Inflammation metabolism, Interleukin-1beta biosynthesis, Interleukin-1beta genetics, Monocytes drug effects, Monocytes metabolism, Prednisolone pharmacology
- Abstract
Glucocorticoids such as prednisolone are used for their anti-inflammatory properties. But there is evidence to suggest that under certain conditions, glucocorticoids have pro-inflammatory effects, for example, enhancement of IL-1beta production. To date, it has been reported that IL-1beta production intensity was associated with single nucleotide polymorphisms at positions -1470, -511, and -31 in the promoter region and at position 3954 in exon 5 of the IL-1beta gene. In the present study, it was examined whether these IL-1beta genotypes were associated with the suppressive effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). A midrange concentration (10(-6) M) of prednisolone suppressed the LPS-induced increase in IL-1beta mRNA expression and protein release, while higher concentrations (10(-5) M, 10(-4) M) exhibited less suppression or had a synergistic stimulative effect on IL-1beta production in certain subjects. Under treatment with 10(-4) M prednisolone, the levels of IL-1beta protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1beta TT(-31), TC(-31), and CC(-31) genotypes were suppressed to 6.0+/-3.4%, 31.4+/-57.0%, and 87.7+/-84.8%, respectively, of the level in prednisolone-untreated control cells (TT(-31) vs. CC(-31), p<0.05). Glucocorticoid-based anti-inflammatory therapy might be less effective in patients with the IL-1beta TC(-31) and CC(-31) genotypes than those with the TT(-31) genotype.
- Published
- 2007
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