Regulation of hepatocyte fate by interferon-γ

Interferon-γ regulation of the human mimecan promoter

The IFNs are a family of secreted glycoproteins that play roles in regulation of antiviral, antiproliferative, and immunomodulatory responses in vertebrate cells. Two types of IFNs have been described, the type I IFNs (α, β, ω, and τ) that are produced by leukocytes and fibroblasts, and the type II IFN (γ) that is produced by T-lymphocytes and natural killer cells in response to infections by v...

Increasing Affinity of Interferon-γ Receptor 1 to Interferon-γ by Computer-Aided Design

We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-γ receptor 1 (IFN-γ-Rx) to increase its affinity to natural ligand IFN-γ, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-γ-Rx/IFN-γ complex to identify 40 receptor residues ...

Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection

Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial replication while preventing an over-exuberant inflammatory response. Interferon (IFN) γ is crucial for activating macrophages and also regulates tissue inflammation. We dissociate these two functions and show that IFN-γ(-/-) memory CD4(+) T cells retain their antimicrobial activity but are unable to suppress infla...

Regulation of Epigenetic Modifiers, Including KDM6B, by Interferon-γ and Interleukin-4 in Human Macrophages

BACKGROUND Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS We investigated steady-state messenger RNA levels of 84 his...

IGF-I regulation by IFN-γ requires STAT-5b TRANSCRIPTIONAL REGULATION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) BY INTERFERON-GAMMA (IFN-γ) REQUIRES STAT-5b