Biomaterial Database

Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone. 2017

Ting-Yun Chuang, and An-Jie Cheng, and I-Ting Chen, and Tien-Yun Lan, and I-Hsuan Huang, and Chung-Wai Shiau, and Chia-Lin Hsu, and Ya-Wen Liu, and Zee-Fen Chang, and Ping-Hui Tseng, and Jean-Cheng Kuo

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan.

The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacterial lipopolysaccharides (LPS). Nevertheless, the extent to which the functional groups of Dex control the excessive activation of inflammatory reactions remains unknown. Furthermore, importantly, the role of Dex in the innate immune response remains unclear. Here we explore the mechanism of LPS-induced TNF-α secretion and reveal p38 MAPK signaling as a target of Dex that is involved in control of tumor necrosis factor-α (TNF-α)-converting enzyme (TACE) activity; that later mediates the shedding of TNF-α that allows its secretion. We further demonstrate that the 11-hydroxyl and 21-hydroxyl groups of Dex are the main groups that are involved in reducing LPS-induced TNF-α secretion by activated macrophages. Blockage of the hydroxyl groups of Dex inhibits immunosuppressant effect of Dex during LPS-induced TNF-α secretion and mouse mortality. Our findings demonstrate Dex signaling is involved in the control of innate immunity.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D008262	Macrophage Activation	The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.	Activation, Macrophage,Activations, Macrophage,Macrophage Activations
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D006878	Hydroxides	Inorganic compounds that contain the OH- group.
D000067996	RAW 264.7 Cells	A transformed macrophage cell line isolated from ASCITES of mice infected with ABELSON MURINE LEUKEMIA VIRUS.	RAW 264.7 Cell Line,264.7 Cell, RAW,264.7 Cells, RAW,Cell, RAW 264.7,Cells, RAW 264.7,RAW 264.7 Cell
D000072198	ADAM17 Protein	A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. It cleaves several other CELL SURFACE PROTEINS, including INTERLEUKIN-1 RECEPTOR TYPE II; TRANSFORMING GROWTH FACTOR ALPHA; L-SELECTIN; MUCIN-1; and AMYLOID BETA-PROTEIN PRECURSOR. It can also function as an activator of the Notch signaling pathway by mediating the cleavage of NOTCH RECEPTORS.	ADAM-17,ADAM-17 Protein,CD156b Antigen,Disintegrin and Metalloproteinase Domain-Containing Protein 17,TACA (Enzyme),TACE (Enzyme),TNF-alpha Convertase,TNF-alpha Converting Enzyme,Tumor Necrosis Factor Alpha Convertase,Tumor Necrosis Factor-alpha Convertase,Tumor Necrosis Factor-alpha Converting Enzyme,ADAM 17 Protein,Antigen, CD156b,Convertase, TNF-alpha,Disintegrin and Metalloproteinase Domain Containing Protein 17,TNF alpha Convertase,TNF alpha Converting Enzyme,Tumor Necrosis Factor alpha Converting Enzyme
D000107	Acetylation	Formation of an acetyl derivative. (Stedman, 25th ed)	Acetylations