Influence of medical illness on body composition and quality of life in geriatric outpatients: a pilot study.
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Aged↗
Biomedical subjects
S X Leng
Publications and source records attributed to S X Leng.
Transforming growth factor-beta stimulates interleukin-11 transcription via complex activating protein-1-dependent pathways.
Studies were undertaken to characterize the mechanism by which transforming growth factor-beta1 (TGF-beta1) stimulates epithelial cell interleukin (IL)-11 production. Nuclear run-on studies demonstrated that TGF-beta1 is a potent stimulator of IL-11 gene transcription. TGF-beta1 also stimulated the luciferase activity in cells transfected with reporter gene constructs containing nucleotides -728 to +58 of the IL-11 promoter. Studies with progressive 5' deletion constructs and site-specific mutations demonstrated that this stimulation was dependent on 2 AP-1 sites between nucleotides -100 and -82 in the IL-11 promoter. Mobility shift assays demonstrated that TGF-beta1 stimulated AP-1 protein-DNA binding to both AP-1 sites. Supershift analysis demonstrated that JunD was the major moiety contributing to AP-1-DNA binding in unstimulated cells and that c-Jun-, Fra-1-, and Fra-2-DNA binding were increased whereas JunD-DNA binding was decreased in TGF-beta1-stimulated cells. The sequence in the IL-11 promoter that contains the AP-1 sites also conferred TGF-beta1 responsiveness, in a position-independent fashion, on a heterologous minimal promoter. Thus, TGF-beta1 stimulates IL-11 gene transcription via a complex AP-1-dependent pathway that is dependent on 2 AP-1 motifs between nucleotides -100 and -82 that function as an enhancer in the IL-11 promoter.
Base Sequence↗
Interleukin-11 inhibits macrophage interleukin-12 production.
IL-12 is a heterodimeric cytokine produced by phagocytic and other cells with important physiologic and pathologic properties. Regulated IL-12 production is crucial for the generation of protective Th1 responses to infectious agents. In contrast, IL-12 excess contributes to the pathogenesis of a variety of autoimmune and inflammatory disorders. To further understand the processes regulating IL-12 production, we determined whether IL-11 regulated monocyte/macrophage production of this cytokine moiety. IL-11 did not alter the IL-12 (p70) production of unstimulated THP-1 monocytic cells or human blood monocytes. It did, however, inhibit, in a dose-dependent fashion, the IL-12 production of IFN-gamma plus Staphylococcus aureus Cowan strain 1-stimulated THP-1 cells and stimulated blood monocytes. This inhibition of IL-12 protein production was associated with a proportionate decrease in IL-12 p35 and p40 mRNA accumulation. Nuclear run-on assays revealed comparable decreases in IL-12 p35 and p40 gene transcription. IL-11 did not similarly regulate monocyte/macrophage production of IL-8 or macrophage inflammatory protein-1alpha (MIP-1alpha) and IL-6 did not similarly inhibit IL-12 elaboration. These studies demonstrate that IL-11 is a potent inhibitor of monocyte/macrophage IL-12 production and that this inhibitory effect is, at least in part, transcriptionally mediated. They also demonstrate that this inhibition is not the result of a generalized suppression of macrophage effector function and that the ability to inhibit monocyte/macrophage IL-12 production is not a generalized property of all IL-6-type cytokines.
Depression, Chemical↗
Interleukin-11.
Interleukin-11 (IL-11) is an IL-6-type cytokine that is produced by a variety of stromal cells including fibroblasts, epithelial cells and osteoblasts. It binds to a multimeric receptor complex which contains an IL-11-specific alpha subunit and a promiscuous 130 kDa beta subunit (gp130). IL-11 stimulates multiple aspects of hematopoiesis and hepatocyte production of acute phase response proteins. It also inhibits the genesis of adipocytes, activates osteoclasts, alters neural phenotype, stimulates tissue fibrosis and regulates chondrocyte, synoviocyte and B cell function. In other settings, IL-11 minimizes tissue injury. This may be the result of its ability to protect clonogenic stem cells, regulate epithelial cell proliferation, inhibit apoptosis and inhibit macrophage cytokine production. Thus, IL-11 appears to play an important role in hematopoiesis, bone metabolism and tissue remodeling and may be an important protector of mucosal surfaces.
Acute-Phase Proteins↗