17.BETA.-Estradiol Enhances Interleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

Abstract

To clarify the mechanism underlying the enhancing effect of 17β-estradiol (E2) on contact hypersensitivity (CHS) and the expression of interferon (IFN)-γ in mice, the mRNA expression levels of interleukin (IL)-18 were evaluated. Female BALB/c mice aged 3 weeks were ovariectomized, administered 3.2 µg of E2, and sensitized by 50 µl of 3% 4-ethoxymethylene-2-phenyl-2-oxazolin-one (OXA). Seven days later, CHS was elicited by the application of 7.5 µl 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-γ 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-γ 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-γ mRNA expression is enhanced in the elicitation phase of CHS.

<i>p</i>-Hydroxybenzoate Esters Enhance Mouse Contact Hypersensitivity

“…Further, we have previously reported that the expression of IFN-γ mRNA of 17β-estradiol-administered mice is enhanced at 6 hr and decreased to the same level with the control mice at 9 hr after the challenge. 15) Similar to our previous observations on 17β-estradiol, 15,22) in mice that were administered butylparaben, the expression of IFN-γ mRNA was increased 6 hr after challenge (Fig. 5b) and the expression of IL-18 mRNA was increased on the seventh day after the sensitization of mice (Fig.…”

“…In our previous report, 22) 17β-estradiol enhances the expression of IL-18 mRNA on the fourth and the seventh day after the sensitization of mice, in other words, before the elicitation of allergy. Besides, 17β-estradiol does not enhance IL-18 mRNA expression after the challenge because the IL-18 mRNA expression of control mice is also induced by the elicitation of allergy.…”