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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alternative activation of macrophages, induced by Th2 cytokines and glucocorticoids, is essential for the proper functioning of anti-inflammatory immune reactions. To this end, alternatively activated macrophages (aaMΦ) express a not yet fully unravelled set of genes including cytokines such as alternative macrophage activation-associated CC-chemokine (AMAC)-1 and pattern recognition molecules such as the scavenger receptor CD163. In order to further characterize the molecular repertoire of aaMΦ, differential gene expression was analyzed by combining subtractive suppression cloning and differential hybridization. We show here that aaMΦ induced by interleukin (IL)-4 overexpress the prototype extracellular matrix (ECM) protein fibronectin on the mRNA and protein level. This overall increase is accompanied by a shift in fibronectin splice variants from an embryonic to a mature pattern. In addition, the expression of another ECM protein, βIG-H3, is also upregulated by IL-4 in aaMΦ. In contrast to IL-4 and in line with its inhibitory effect on wound healing, dexamethasone exerts a strongly suppressive effect on fibronectin and βIG-H3 expression. In conclusion, overexpression of ECM proteins induced by IL-4 in macrophages suggests that aaMΦ may be involved in ECM deposition and tissue remodelling during the healing phase of acute inflammatory reactions and in chronic inflammatory diseases.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 61 (2005), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alternatively activated macrophages (Mφ2) are induced by Th2 cytokines and by glucocorticoids (GC), and can be distinguished from classically activated effector macrophages (Mφ1) on the basis of their anti-inflammatory properties. In addition, Mφ2 are involved in Th2/Th1 skewing, enhance antigen uptake and processing and support tissue remodelling and healing. In order to elucidate the heterogeneity of Mφ2 population systematically, we analysed a number of genes involved in extracellular matrix (ECM) remodelling, inflammation and phagocytosis in Mφ2 populations generated with interleukin-4 (IL-4) or GC. Using real-time polymerase chain reaction, we demonstrated that the ECM component, tenascin-C, is stimulated by IL-4, whereas it is suppressed by dexamethasone. The ECM remodelling enzymes – MMP-1 and MMP-12 – and tissue transglutaminase (TG) showed a similar regulation pattern. FXIIIa, another putative Mφ2-associated TG, was synergistically regulated by IL-4 and GC. Enzyme-linked immunosorbent assay analysis revealed that the production of Mφ2-associated chemokines, AMAC-1, MCP-4 or TARC, was induced by IL-4 and was modulated by GC. Phagocytosis of opsonized and non-opsonized particles was stimulated by GC, whereas IL-4 had only a modulatory effect, what may be partially explained by the expression pattern of hMARCO, a scavenger receptor for non-opsonized particles, that was strongly and selectively induced by GC. In conclusion, stimulation of Mφ with IL-4 and GC regulate antagonistically the expression of ECM remodelling-related molecules and phagocytosis of opsonized and non-opsonized particles.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 60 (2004), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin-17E (IL-17E) (IL-25) is a recently identified cytokine capable to induce Th2-associated cytokine production (IL-5 and IL-13) and T helper 2 (Th2)-type pathologies in animal models. The IL-17E-responsive cell population in vivo was described to be a further uncharacterized non-T-, non-B-splenic accessory cell. Despite the identification of IL-17BR as the receptor for IL-17E, the cell population expressing IL-17BR has hitherto not been identified. Here, we show that human monocyte-derived Th2-skewed antigen-presenting cells (APC2) express membrane-bound and soluble forms of IL-17BR on the mRNA and protein level upon stimulation with IL-4, IL-10, IL-13 or transforming growth factor-βin vitro. These results indicate that IL-17BR-expressing APC2s may mediate the development of the IL-17E-mediated immunological reaction patterns observed in vivo.
    Type of Medium: Electronic Resource
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