Production of interleukin (IL)-10, a major immunoregulatory cytokine, by phagocytes during clearance of apoptotic cells is critical to ensuring cellular homeostasis and suppression of autoimmunity. Little is known about the regulatory mechanisms in this fundamental process. We report that IL-10 production stimulated by apoptotic cells was regulated at the point of transcription in a manner dependent on p38 mitogen-activated protein kinase, partially on the scavenger receptor CD36, and required cell-cell contact but not phagocytosis. By using a reporter assay, we mapped the apoptotic-cell-response element (ACRE) in the human IL10 promoter and provide biochemical and physiological evidence that ACRE mediates the transcriptional activation of IL10 by pre-B cell leukemia transcription factor-1b and another Hox cofactor Pbx-regulating protein 1 in response to apoptotic cells. This study establishes a role of two developmentally critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the immune system.
Interleukin-12 (IL-12) is a heterodimeric cytokine composed of the p35 and p40 subunits. It is produced by antigen-presenting cells and plays a critical role in host defense against intracellular microbial infection and control of malignancy via its ability to stimulate both innate and adaptive immune effector cells. The potency of IL-12 renders itself to stringent regulation of the timing, locality and magnitude of its production during an immune response. Subversion of the delicate control and balance frequently leads to immunologic disorders. In this article, we provide an update, since our last review of the subject four years ago, on recent advances in: (1) uncovering of novel activities of IL-12 and related molecules in various immunological settings and models; and (2) dissection of the physiological pathways involved in the modulation of IL-12 production by pathogens and immune regulators. The increased understanding of IL-12 immunobiology and expression will likely benefit the development of therapeutic modalities to correct immune dysfunctions.
Wound compression and fixation are important to reduce scarring. Numerous postoperative treatments have been developed to reduce scar formation; however, a simple and effective device that improves the appearance and histochemical properties of incisional scars is needed. Therefore, the authors have devised a novel method, negative-pressure fixation, that applies negative pressure inside polyurethane foam covered with film. In the present study, negative-pressure fixation was applied to incisional wounds resulting from the insertion of a tissue expander in patients undergoing two-stage breast reconstruction. The authors aimed to evaluate the effects of negative-pressure fixation on scar appearance and histochemical properties in comparison to those for film dressing without negative pressure. A prospective, open-label, randomized, single-center study was performed. A half-side test was conducted on the incisional scar resulting from tissue expander insertion during breast reconstruction after mastectomy in 13 female patients. The dressings on both sides of the scar were replaced once per week until the tissue expander was adequately inflated. The outcomes were assessed 6 months later. Scars were photographed before the second operation and were evaluated using a visual analogue scale. All scars were removed and resutured during the final operation, allowing a histochemical analysis. The mean visual analogue scale score for the negative-pressure fixation side was significantly lower compared with that for the film dressing side (p = 0.0025). In addition, the scar on the negative-pressure fixation side was significantly narrower (p = 0.0015). Thus, negative-pressure fixation is a simple and effective device for improving the appearance and histochemical properties of incisional scars.
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