17beta-Estradiol Enhances lnterleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

摘要

To clarify the mechanism underlying the enhancing effect of 17beta-estradiol (E2) on contact hypersensitivity (CHS) and the expression of interferon (IFN)-y in mice, the mRNA expression levels of interleukin (IL)-18 were evaluated. Female BALB/c mice aged 3 weeks were ovariectomized, administered 3.2 |ig of E2, and sensitized by 50 mul of 3% 4-ethoxymethylene-2-phenyl-2-oxazolin-one (OXA). Seven days later, CHS was elicited by the application of 7.5mul of 1% OXA on the ear auricles. The auricles, cervical lymph nodes and spleens were excised, and gene expression was evaluated by reverse transcription-polymerase chain reaction. E2 enhanced the expression of IL-18 mRNA in the spleen on the following day and in the ear auricles on days 4 and 7 after sensitization with OXA. The preadministration of an antibody against IL-18 receptor suppressed the CHS and reduced IFN-y mRNA expression in E2-administered mice. IL-18 was present in the dermis of the ear skin and absent in the epidermis. E2 also enhanced the expression of IFN-y and IL-18 mRNAs in splenocytes cultured with lipopolysaccharide (LPS). IL-18 protein was detected by flow cytometry in CD4~+, CD8~+ and NKG2~+ lymphocytes among splenocytes cultured with LPS. These results suggest that E2 enhances lymphocyte activation in the sensitization phase of CHS, and that IFN-y mRNA expression is enhanced in the elicitation phase of CHS.