Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells

Interferon-γ(IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells(BMECs) in vitro. In this study, we investigated the mechanisms underlying pthe malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ(10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4(CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene(c-Abl) and histone deacetylase 2(HDAC2). The HDAC2 inhibitor, valproate(VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

A corn straw-based diet increases release of inflammatory cytokines in peripheral blood mononuclear cells of dairy cows

Recent studies have shown that diet can affect the body＇s immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells （PBMCs）, and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage （MF）- or corn straw （CS）-based diets. Ex- pression profile analysis was used to detect the differentially expressed genes （DEGs） from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24027 analyzed probes. Gene ontology （GO） and pathway analysis of DEGs suggested that these genes （especially genes coding cytokines, chemokine and its receptors） are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 （IL-2）, IL-6, IL-10, IL-12, leptin （LEP）, interferon-γ （IFN-γ）, transforming growth factor-βl （TGF-β1）, and tumor necrosis factor-α （TNF-α） in peripheral blood by enzyme-linked immunosorbent assay （ELISA） and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows＇ PBMCs, and milk protein content may be affected by cytokines.