Bisphenol A Promotes IL-4 Production by Th2 Cells

Abstract

Background: It has been proposed that estrogen plays an important role in modulating the Th1/Th2 cytokine balance. From this viewpoint, chemicals with estrogenic responses were expected to possess similar immunoregulatory roles which have not been defined to date. To address this, we studied the effects of one of the estrogenic chemicals, bisphenol A (BPA), on the in vitro production of Th1 and Th2 cytokines. Methods: Mesenteric lymph node cells from Trichinella spiralis (Ts)-infected mice were incubated with serialfold dilutions of BPA under stimulation with Ts antigen. The Th2 cytokine production in the supernatant was determined by ELISA. The Th2 cytokine production by mesenteric lymph node cells from Ts-infected mice inoculated orally with BPA was compared with that of uninoculated mice infected with Ts. Results: The antigen-stimulated interleukin (IL)-4 production by Th2-dominant mesenteric lymph node cells from Ts-infected mice increased significantly by addition of 3 µM of BPA. The IL-5 production was not affected. The production of IL-4, but not that of IL-5, by splenocytes of Th2-skewed Leishmania major-infected BALB/c mice increased at concentrations of 3 and 10 µM of BPA. However, the interferon gamma production was not affected by BPA in Th1-skewed L. major-infected C57BL/6 mice. The production of IL-4 and IL-10, but not that of IL-13, markedly increased in Ts-infected mice inoculated orally with BPA. Conclusions: We demonstrated that the IL-4 production was increased both in vitro and in vivo by treatment with BPA. This suggests that BPA might cause allergic diseases by stimulating the IL-4 production by Th2 cells.

Orally Administered Bisphenol A Disturbed Antigen Specific Immunoresponses in the Naïve Condition

“…(intra peritoneal) administration of BPA. Tian 21) reported that Th2-type cytokine production by mesenteric lymph node cells increased markedly in Trichinella spiralis-infected mice inoculated orally with BPA. Our results indicate that the inhibitory effect of BPA on cytokine secretion was more effective on IL-4 than IFN-, and that therefore the immune responses developed a tendency to a Th1-type reaction, although the effects were not very strong (Fig.…”

“…Some reports have indicated that the exposure of mice to BPA affected their antigen-specific immune responses. Tian 21) suggested that the production of Th2-type cytokines y To whom correspondence should be addressed. Fax: +81-29-838-8055; E-mail: yuko@affrc.go.jp Abbreviations: APCs, antigen presenting cells; BPA, bisphenol A; DMSO, dimethyl sulfoxide; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; IFN, interferon; mAb, monoclonal antibody; XEs, xenoestrogens markedly increased in Trichinella spiralis infected mice inoculated orally with BPA.…”

Bisphenol A: Understanding Its Health Effects from the Studies Performed on Model Organisms

“…The authors inferred that BPA does not selectively activate the Th1 or Th2 path. BPA also enhances Th1 or Th2 response in vivo, depending on the doses [74,77]. In addition, prenatal exposure to BPA was shown to augment both Th1 and Th2 responses in adulthood [74].…”

Bisphenol A in combination with TNF-α selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity

“…Genomic DNA was digested and removed using an RNase-Free DNase Kit (Qiagen). First strand cDNA was synthesized using oligo (dT) [12][13][14][15][16][17][18] primer (Invitrogen, Carlsbad, CA, USA) and the Omniscript RT Kit (Qiagen). The synthesized cDNA was thermocycled for PCR amplification with 1 mM each primer and 1.5 U of Taq polymerase.…”

“…[14][15][16] BPA was reported to enhance IL-4 production by T helper (Th) 2 cells in vitro while also enhancing the Th2 and Th1 immune responses, depending on the doses of BPA administered in vivo. 17,18 These experimental studies have indicated that BPA may help trigger allergic responses. However, the precise mechanism by which BPA regulates the Th responses has remained elusive.…”