ABSTRACT
The Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway genes along with suppressors of cytokine signalling (SOCS) family genes play a crucial role in controlling cytokine signals in the mammary gland and thus mammary gland development. Mammary gene expression studies showed differential expression patterns for all the JAK-STAT pathway genes. Gene expression studies using qRT-PCR revealed differential expression of SOCS2, SOCS4, and SOCS5 genes across the lactation cycle in dairy cows. Using genotypes from 1,546 Australian Holstein-Friesian bulls, a statistical model for an association analysis based on SNPs within 500 kb of JAK-STAT pathway genes, and SOCS genes alone was constructed. The analysis suggested that these genes and pathways make a significant contribution to the Australian milk production traits. There were 24 SNPs close to SOCS1, SOCS3, SOCS5, SOCS7, and CISH genes that were significantly associated with Australian Profit Ranking (APR), Australian Selection Index (ASI), and protein yield (PY). This study supports the view that there may be some merit in choosing SNPs around functionally relevant genes for the selection and genetic improvement schemes for dairy production traits.
ABSTRACT
BACKGROUND: Propolis is a honeybee product that has been used in traditional medicine for antioxidant, immune-stimulating, anti-inflammatory and anti-cancer effects. Here, the potential of the topical application of a crude ethanolic extract of Sydney propolis to protect against UV-radiation-induced impairments associated with an increased risk of photocarcinogenesis has been tested in the hairless mouse. METHODS: Solutions providing between 10 and 200 mg/kg propolis were applied to the skin following UV irradiation. The inflammation from exposure to UV (290-400 nm) was quantitated by measurement of increased skinfold thickness; lipid peroxidation was assayed by the induction of thiobarbituric acid reactive species in the skin; immune function was measured by the contact hypersensitivity (CHS) reaction and supported by the changes in epidermal cytokine expression. RESULTS: Propolis protected significantly and dose-dependently against both sunburn oedema and the suppression of CHS, and (at 100 mg/kg) against lipid peroxidation. The overexpression of IL-10 and the depletion of IL-12 characteristic of photoimmune suppression were markedly reduced by propolis. Further, the upregulation of IL-6 was decreased, and the associated induction of haem oxygenase was shown to play a role in propolis skin protection. CONCLUSIONS: Sydney propolis was able to effectively reduce cutaneous inflammation, immunosuppression and lipid peroxidation induced by UV exposure. It is concluded that Sydney propolis might have strong beneficial protective effects against photodamage and skin cancer development in humans.
Subject(s)
Immunosuppression Therapy , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Propolis/therapeutic use , Radiodermatitis/prevention & control , Skin/drug effects , Skin/radiation effects , Animals , Cytokines/metabolism , Dermatitis, Contact/etiology , Dermatitis, Contact/immunology , Enzyme Inhibitors/pharmacology , Female , Flavonoids/analysis , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/metabolism , Metalloporphyrins/pharmacokinetics , Mice , Mice, Hairless , Oxazolone/pharmacology , Propolis/administration & dosage , Propolis/chemistry , Protoporphyrins/pharmacokinetics , Radiodermatitis/metabolism , Radiodermatitis/pathology , Skin/immunology , Skin/metabolism , Skin/pathology , Skinfold Thickness , Sunburn/metabolism , Sunburn/pathology , Sunburn/prevention & control , Terpenes/analysis , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Previous studies have found that signaling by the estrogen receptor-beta (Er-beta) attenuated solar-simulated UV radiation (SSUV)-induced immunosuppression. This study seeks evidence for a common mechanism for this immunoprotection for both Er-beta signaling and irradiation with the UVA waveband. In Skh:hr-1 hairless mice, the immunoprotection afforded by UVA exposure against subsequent UVB or cis-urocanic acid suppression of contact hypersensitivity (CHS) was abrogated by treatment with the antiestrogen, ICI 182,780. Furthermore, in normal C57BL mice, UVA enrichment of UVA/UVB sources provided protection against UVB-suppressed CHS and upregulated epidermal IL-10 expression, but this protection was inhibited in Er-beta-/- mice. These observations indicated that the immunoprotective response to UVA was dependent on Er-beta signaling. As earlier studies have established that UVA photoimmune protection depends on the induction of the stress enzyme, heme oxygenase (HO)-1, its activity was examined relative to Er-beta. Immunoprotection against SSUV by 17-beta-estradiol was prevented by inhibiting HO enzyme activity; immunoprotection against cis-urocanic acid by carbon monoxide (HO product) was prevented by ICI 182,780. In addition, the HO-1 gene was unresponsive to UVA induction in Er-beta-/- mice. Therefore, HO-1 inducibility and Er-beta signaling are interdependent requisite responses to the UVA waveband for its immunoprotective action against UVB exposure.
Subject(s)
Estrogen Receptor beta/genetics , Heme Oxygenase-1/genetics , Immune Tolerance/radiation effects , Signal Transduction/radiation effects , Ultraviolet Rays , Animals , Enzyme Inhibitors/pharmacology , Epidermis/immunology , Epidermis/pathology , Epidermis/radiation effects , Estradiol/analogs & derivatives , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Estrogen Receptor beta/antagonists & inhibitors , Estrogen Receptor beta/metabolism , Female , Fulvestrant , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/metabolism , Immune Tolerance/immunology , Interleukin-10/metabolism , Metalloporphyrins/pharmacology , Mice , Mice, Hairless , Mice, Inbred C57BL , Mice, Mutant Strains , Protoporphyrins/pharmacology , RNA, Messenger/metabolism , Signal Transduction/immunology , Urocanic Acid/pharmacologyABSTRACT
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.
