Estrogen receptor-beta signaling protects epidermal cytokine expression and immune function from UVB-induced impairment in mice

Abstract

A previous study in the hairless mouse, in which the photoimmune protective properties of a topical phytoestrogen or 17-beta-estradiol were abrogated by the estrogen receptor antagonist ICI 182,780, revealed that estrogen receptor (Er) signaling is involved in the regulation of the suppression of immune function by UVB (290-320 nm) radiation. Here we identify the expression of Er-beta but not Er-alpha mRNA in hairless mouse skin, whereas Er-alpha and Er-beta mRNA were present in normal haired mouse skin. This suggests that the non-classical estrogen target Er-beta is involved in the photoimmune modulation, and is consistent with Er-alpha being more closely associated with hair growth control, as indicated by other studies. In mice with a null mutation for Er-beta, there was a significant exacerbation of the solar simulated UV (290-400 nm)-induced suppression of contact hypersensitivity. Immunohistochemical analysis revealed that the Er-beta deficiency inhibited the normally immunoprotective upregulation by the UVA (320-400 nm) waveband of the epidermal expression of the cytokines IFN-gamma and IL-12. Er-beta deficiency also significantly increased the UVB-induced expression of the immunosuppressive cytokine IL-10. Thus Er signalling via the Er-beta is evidently a major regulator of the UVA and UVB waveband interactions that determine the skin's immune functional status, and achieves this by normalization of the cutaneous cytokine array in the UV-irradiated skin.

Effects of ultraviolet radiation exposure on FOXP3+ infiltration in cutaneous squamous cell carcinoma and basal cell carcinoma

“…c) . Although signaling through the estrogen receptor‐beta was protective in UV‐induced skin cancer , evidence showed that enhanced FOXP3 expression and Treg cell function were observed in pregnant, estrogen‐treated mice . George et al .…”

“…5c) (22)(23)(24)(25). Although signaling through the estrogen receptor-beta was protective in UV-induced skin cancer (26), evidence showed that enhanced FOXP3 expression and Treg cell function were observed in pregnant, estrogen-treated mice (24,25). George et al showed that UVA-treated mouse splenocytes could increase the frequency of FOXP3+ splenic T cells, after injected intravenously into syngeneic mice (27).…”

The Sound of a Buk (Korean Traditional Drum) Attenuates Anaphylactic Reactions by the Activation of Estrogen Receptor-β

“…ER-β activation contributes to the down-regulation of HIF-1α and VEGF in the brain [12]. Furthermore, ER signaling is also involved in the suppression of immune function [33]. Our results show that the down-regulation of ER-β mRNA levels by compound 48/80 were inhibited by exposure to Buk music, indicating Buk music inhibited anaphylaxis by inhibiting the up-regulation of HIF-1α, VEGF, and TNF-α following ER-β activation.…”

Targeting Estrogen Receptor-β for the Prevention of Nonmelanoma Skin Cancer

“…Cho and colleagues performed a series of experiments suggesting a role for ERβ in UV-induced skin cancer. Expression of immunoprotective up-regulation of UVA-induced epidermal expression of interferon-γ and interleukin-12 (IL12) was inhibited in Erb -null mice as compared to controls (16). Erb -null mice exposed to UVB also exhibited enhanced expression of the immunosuppressive cytokine IL10 (16).…”

“…Expression of immunoprotective up-regulation of UVA-induced epidermal expression of interferon-γ and interleukin-12 (IL12) was inhibited in Erb -null mice as compared to controls (16). Erb -null mice exposed to UVB also exhibited enhanced expression of the immunosuppressive cytokine IL10 (16). Using an ERβ antagonist or Erb -null mice, they also demonstrated that chemical antagonism of ERβ or genetic disruption of ERβ following irradiation with UV led to increased tumor growth that was due in part to altered immune function (17).…”