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Hyper-inflammatory responses triggered by intracellular reactive oxygen species (ROS) can lead to a variety of diseases, including sepsis and colitis. However, the regulators of this process remain poorly defined. In this study, we demonstrate that c-Src is a negative regulator of cellular ROS generation through its binding to p47phox. This molecule also competitively inhibits the NADPH oxidase complex (NOX) assembly. Furthermore, we developed the schizophyllan (SPG)-c-Src SH3 peptide, which is a β-1,3-glucan conjugated c-Src SH3-derived peptide composed of amino acids 91-108 and 121-140 of c-Src. The SPG-SH3 peptide has a significant therapeutic effect on mouse ROS-mediated inflammatory disease models, cecal-ligation-puncture-induced sepsis, and dextran sodium sulfate-induced colitis. It does so by inhibiting the NOX subunit assembly and proinflammatory mediator production. Therefore, the SPG-SH3 peptide is a potential therapeutic agent for ROS-associated lethal inflammatory diseases. Our findings provide clues for the development of new peptide-base drugs that will target p47phox., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Extracellular matrix (ECM) proteins containing cell‐attachable Arg‐Gly‐Asp (RGD) sequences exhibit variable bridging and non‐bridging in fibronectin‐collagen and laminin‐collagen complexes that can regulate inflammation, tissue repair, and wound healing. In this study, linking molecule‐mediated conjugation of 1D magnetic nanocylinders (MNCs) to material surfaces pre‐decorated with gold nanospheres (GNSs) is performed, thereby yielding RGD‐coated MNCs (RGD‐MNCs) over RGD‐coated GNSs (RGD‐GNSs) in a non‐bridging state. The RGD‐MNCs are drawn closer to the RGD‐GNSs via magnetic field‐mediated compression of the linking molecules to establish the bridging between them. Relative proportion of the RGD‐MNCs to the RGD‐GNSs is optimized to yield effective remote stimulation of integrin binding to variably bridged RGDs similar to that of invariably bridged RGDs used as a control group. Remote manipulation of the RGD bridging facilitates the attachment structure assembly of macrophages that leads to pro‐healing/anti‐inflammatory phenotype acquisition. In contrast, the non‐bridged RGDs inhibited macrophage attachment that acquired pro‐inflammatory phenotypes. The use of various nanomaterials in constructing heterogeneous RGD‐coated materials can further offer various modes in remote switching of RGD bridging and non‐bridging to understand dynamic integrin‐mediated modulation of macrophages that regulate immunomodulatory responses, such as foreign body responses, tissue repair, and wound healing. [ABSTRACT FROM AUTHOR]