ABSTRACT
BACKGROUND: This study was performed in response to the rapid propagation of HIV/AIDS across Iran and its status in this region. Accordingly, an evidence-based program is required to combat this disease. OBJECTIVES: The present study estimated the prevalence of HIV/AIDS in East Azerbaijan (population: 3,724,000). MATERIALS AND METHODS: We created a database of all positive cases from 1987 to 2012. We also analyzed and described the epidemiological status of HIV/AIDS during a 25-year period by using SPSS. RESULTS: In East Azerbaijan, 371 HIV/AIDS cases have been reported, i.e. 1 case per 10,000 population. The vast majority of reported cases (91%, n =338) were men, whereas only 9% (n = 33) were women. The mean age of patients was 30.8 ± 12.3 years. Unsafe drug injection (59%, n = 219) and sexual interaction (13%, n = 48) were the two major modes of HIV transmission. In addition, 7% (n = 25) of patients have been diagnosed with HIV, hepatitis B Virus, and hepatitis C virus simultaneously. Moreover, 60% (n = 205) of men were infected via drug injection, while 82% (n = 27) of women were infected via unprotected sexual interaction (P < 0.001). CONCLUSIONS: The results indicate a rapid increase in the number of HIV/AIDS cases in East Azerbaijan, necessitating immediate attention and strategies to combat the rapid spread of the disease. Development of provincial and national HIV/AIDS strategies demands more accurate and comprehensive HIV/AIDS surveillance.
ABSTRACT
IL-27, a member of the IL-12 cytokine family, is a key immunoregulatory cytokine produced predominantly by monocytic cells and mediates innate and adaptive immune responses. IL-27 has been shown to be produced by human monocytic cells primed with IFN-γ and in response to a second stimulus such as LPS. In this study, we show for the first time that IFN-γ alone without any second stimulus can induce IL-27p28 gene expression and IL-27 protein production by human monocytic cells. The signaling pathways that govern IL-27 production in general, and particularly following stimulation of monocytic cells with IFN-γ are not known. We investigated the signaling pathways governing the regulation of IL-27 protein and its subunit IL-27p28 following stimulation with IFN-γ in primary human monocytic cells. Our results suggest that IFN-γ-mediated IL-27 protein but not IL-27p28 gene expression is positively regulated by the C-Jun N-terminal kinases (JNK), mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinase (PI3K), independent of the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) signaling in primary human monocytes.
Subject(s)
Interferon-gamma/pharmacology , Interleukin-27/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Monocytes/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Anthracenes/pharmacology , Blotting, Western , Cells, Cultured , Chromones/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Enzyme-Linked Immunosorbent Assay , Gene Expression/drug effects , Humans , Interleukin-27/genetics , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Janus Kinases/metabolism , Lipopolysaccharides/pharmacology , Monocytes/cytology , Monocytes/metabolism , Morpholines/pharmacology , Phosphoinositide-3 Kinase Inhibitors , Reverse Transcriptase Polymerase Chain Reaction , STAT Transcription Factors/metabolismABSTRACT
Interferon (IFN)-γ is a potent stimulator of the IL-12 family Th1 cytokines, including IL-12/23p40 and IL-23, responsible for coordinating the innate and adaptive immune responses. Our results show that IFN-γ induced the production of IL-12/23p40 and IL-23p19 mRNA as well as IL-12p40 and IL-23 proteins in primary human monocytes isolated by positive selection through anti-CD14 microbeads. These results were confirmed by IFN-γ stimulation of CD14-activated monocytes resulting in IL-12/23p40 and IL-23 production. We investigated the signaling pathways governing the regulation of IL-23 and its subunits IL-23p40 and IL-23p19 following IFN-γ stimulation. We observed a differential regulation of IL-23p19, IL-12/23p40, and IL-23 following IFN-γ stimulation. IFN-γ-induced IL-23 and IL-12/23p40 expression was positively regulated by the p38 mitogen-activated protein kinases (MAPKs), independent of the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) signaling. In contrast, IL-12 and IL-23 were negatively regulated by the Jak/STAT, phosphatidylinositol 3-kinase (PI3K), and the c-Jun-N-terminal kinase (JNK) MAPKs in IFN-γ-stimulated monocytes. Overall, our results suggest for the first time a differential positive regulation of IL-12p40 and IL-23 by p38 MAPKs independent of the Jak/STAT pathways and negative regulation by the Jak/STAT, JNK, and PI3K pathways in CD14-activated primary human monocytes stimulated with IFN-γ.
