Interferon-related Genes Research Articles

Interferon-related and other immune genes are downregulated in peripheral blood leukocytes in the luteal phase of the menstrual cycle.

Interaction between the endocrine and the immune systems has been suggested by observations of sexual dimorphism of the immune response, differential susceptibility to autoimmunity between the sexes, changes in autoimmune disease activity during the menstrual cycle and in pregnancy and in vitro studies of hormonal influence on cytokine production.We hypothesized that if there is hormonal regulation of the immune response, this would be manifest in peripheral blood leukocytes (PBLs) at different phases of the menstrual cycle. In this study, we describe gene profiling of PBLs from the follicular and luteal phases of the menstrual cycle. We observe important differences in immune gene expression, with significant down-regulation of the Th1 immune response in the luteal phase. A significant number of interferon (IFN)-related genes are amongst the downregulated genes. These results support significant hormonal regulation of the immune system and may have therapeutic implications in diseases of autoimmunity in women.

Crystallographic Characterization of the DNA-Binding Domain of Interferon Regulatory Factor-2 Complexed with DNA

Interferon regulatory factors (IRFs) are transcription factors for interferon-related genes, which manifest both antiviral and tumor-suppressor activities and regulate cell growth in response to DNA damage. For the transcription initiation of the interferon-β gene, IRFs form a macromolecular assembly bound to the promoter DNA, referred to as an enhancesome, together with several other transcription factors and DNA-binding proteins. The three-dimensional structure of IRF–DNA complex would provide insights into the structure and function of the enhancesome. In this study, we crystallized the DNA-binding domain of interferon regulatory factor-2 complexed with a DNA fragment. The crystals reproducibly grew by the vapor diffusion technique with 2-methyl-pentanediol from solutions containing small detergents, such asn-octyl-β-d-glucoside. Cryocrystallographic experiments showed that crystals belong to space groupP212121witha= 90.66 Å,b= 101.01 Å,c= 171.58 Å and diffract up to 2.8 Å resolution. The absorption measurements of a solution in which the crystals were dissolved indicate that the DNA-binding domain binds to the DNA as a dimer. The calculated values of the solvent contents suggest that the protein–DNA complexes form a multimer in the crystal. These features may reflect the association of the complexes in the enhancesome.