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Background. The HIN-200 family genes in humans have been linked to several autoimmune diseases—particularly to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, its human counterpart gene cluster, the Ifi200 family in mice, has been linked to spontaneous arthritis disease (SAD). However, many immune-mediated diseases (including RA and SLE) show gender difference. Understanding whether or not and how these genes play a role in sex difference in immune-mediated diseases is essential for diagnosis/treatment. Methods. This study takes advantage of the whole genome gene expression profiles of recombinant inbred (RI) strain populations from female and male mice to analyze potential sex differences in a variety of genes in disease pathways. Expression levels and regulatory QTL of Ifi200 family genes between female and male mice were first examined in a large mouse population, including RI strains derived from C57BL/6J, DBA/2J (BXD), and classic inbred strains. Sex similarities and differences were then analyzed for correlations with gene expression levels between genes in the Ifi200 family and four selected gene sets: known immune Ifi200 pathway-related genes, lupus-relevant genes, osteoarthritis- (OA-) and RA-relevant genes, and sex hormone-related genes. Results. The expression level of Ifi202b showed the most sex difference in correlation with known immune-related genes (the P value for Ifi202b is 0.0004). Ifi202b also showed gender difference in correlation with selected sex hormone genes, with a P value of 0.0243. When comparing coexpression levels between Ifi200 genes and lupus-relevant genes, Ifi203 and Ifi205 showed significant sex difference (P values: 0.0303 and 0.002, resp.). Furthermore, several key genes (e.g., Csf1r, Ifnb1, IL-20, IL-22, IL-24, Jhdm1d, Csf1r, Ifnb1, IL-20, IL-22, IL-24, and Tgfb2 that regulate sex differences in immune diseases) were discovered. Conclusions. Different genes in the Ifi200 family play different roles in sex difference among dissimilar pathways of these four gene groups.

Colitis is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases. The present study aimed to examine the molecular mechanisms underlying aloperine-mediated colitis protection. We found that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS) based on body weight, disease activity index, colonic length, and spleen index. Aloperine also effectively attenuated DSS-induced intestinal inflammation based on the pathological score and myeloperoxidase expression and activity in colon tissues. In addition, aloperine regulated T-cell proportions and promoted Foxp3 expression in the spleens and mesenteric lymph nodes of DSS-induced colitis mice and in the spleens of the Foxp3GFP mice. Aloperine inhibited Jurkat and mouse naïve T-cell apoptosis. Furthermore, aloperine inhibited PI3K/Akt/mTOR signaling and upregulated PP2A expression in the DSS-induced colitis mice and in Jurkat cells, but LB-100 (PP2A inhibitor) resulted in an elevated Akt activity in Jurkat cells, activated T-cells, and human splenic mononuclear cells. Aloperine inhibited T-cell and lymphocyte proliferation, but LB-100 reverse these effects. In conclusion, aloperine regulates inflammatory responses in colitis by inhibiting the PI3K/Akt/mTOR signaling in a PP2A-dependent manner.

Background: The HIN-200 family genes in humans have been linked to several autoimmune diseases-particularly to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, its human counterpart gene cluster, the Ifi200 family in mice, has been linked to spontaneous arthritis disease (SAD). However, many immune-mediated diseases (including RA and SLE) show gender difference. Understanding whether or not and how these genes play a role in sex difference in immune-mediated diseases is essential for diagnosis/treatment.Methods: This study takes advantage of the whole genome gene expression profiles of recombinant inbred (RI) strain populations from female and male mice to analyze potential sex differences in a variety of genes in disease pathways. Expression levels and regulatory QTL of Ifi200 family genes between female and male mice were first examined in a large mouse population, including RI strains derived from C57BL/6J, DBA/2J (BXD), and classic inbred strains. Sex similarities and differences were then analyzed for correlations with gene expression levels between genes in the Ifi200 family and four selected gene sets: known immune Ifi200 pathway-related genes, lupus-relevant genes, osteoarthritis- (OA-) and RA-relevant genes, and sex hormone-related genes.Results: The expression level of Ifi202b showed the most sex difference in correlation with known immune-related genes (the P value for Ifi202b is 0.0004). Ifi202b also showed gender difference in correlation with selected sex hormone genes, with a P value of 0.0243. When comparing coexpression levels between Ifi200 genes and lupus-relevant genes, Ifi203 and Ifi205 showed significant sex difference (P values: 0.0303 and 0.002, resp.). Furthermore, several key genes (e.g., Csf1r, Ifnb1, IL-20, IL-22, IL-24, Jhdm1d, Csf1r, Ifnb1, IL-20, IL-22, IL-24, and Tgfb2 that regulate sex differences in immune diseases) were discovered.Conclusions: Different genes in the Ifi200 family play different roles in sex difference among dissimilar pathways of these four gene groups. [ABSTRACT FROM AUTHOR]

The effects of C-phycocyanin (C-PC) on atherosclerosis and the regulatory effects of CD59 gene on anti-atherosclerotic roles of C-PC were investigated. Apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into four groups: control group, C-PC treatment group, CD59 transfection group and C-PC+CD59 synergy group. The mice were fed with high-fat-diet and treated with drug intervention at the same time. Results showed the atherosclerotic mouse model was successfully established. CD59 was over-expressed in blood and tissue cells. Single CD59 or C-PC could reduce blood lipid levels and promote the expression of antiapoptotic Bcl-2 but inhibit pro-apoptotic Fas proteins in endothelial cells. The expression levels of cell cycle protein D1 (Cyclin D1) and mRNA levels of cyclin dependent protein kinase 4 (CDK4) in smooth muscle cells were restrained by CD59 and C-PC. CD59 or C-PC alone could inhibit the formation of atherosclerotic plaque by suppressing MMP-2 protein expression. In addition, C-PC could promote CD59 expression. So both CD59 and C-PC could inhibit the progress of atherosclerosis, and the anti-atherosclerotic effects of C-PC might be fulfilled by promoting CD59 expression, preventing smooth muscle cell proliferation and the apoptosis of endothelial cells, reducing blood fat levels, and at last inhibiting the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Unlike type 2 diabetes which is caused by the loss of insulin sensitivity, type 1 diabetes (T1D) is manifested by the absolute deficiency of insulin secretion due to the loss of β mass by autoimmune response against β-cell self-antigens. Although significant advancement has been made in understanding the pathoetiology for type 1 diabetes, the exact mechanisms underlying autoimmune- mediated β-cell destruction, however, are yet to be fully addressed. Accumulated evidence demonstrates that endoplasmic reticulum (ER) stress plays an essential role in autoimmune-mediated β-cell destruction. There is also evidence supporting that ER stress regulates the functionality of immune cells relevant to autoimmune progression during T1D development. In this paper, we intend to address the role of ER stress in autoimmune-mediated β-cell destruction during the course of type 1 diabetes. The potential implication of ER stress in modulating autoimmune response will be also discussed. We will further dissect the possible pathways implicated in the induction of ER stress and summarize the potential mechanisms underlying ER stress for mediation of β-cell destruction. A better understanding of the role for ER stress in T1D pathoetiology would have great potential aimed at developing effective therapeutic approaches for the prevention/intervention of this devastating disorder. [ABSTRACT FROM AUTHOR]