Biomaterial Database

HMGB1 modulates inflammatory responses in LPS-activated macrophages. 2007

M El Gazzar

Deparment of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. melgazza@wfubmc.edu

OBJECTIVE As a late mediator of inflammation, high mobility group box 1 protein (HMGB1) amplifies the inflammatory responses to tissue injury and infection by inducing and extending the production of proinflammaory cytokines. The aim was to investigate whether HMGB1 mediates such effects by affecting the production of anti-inflammatory mediators. METHODS The murine macrophage RAW 264.7 cells were stimulated with 0.5 microg/ml of LPS and the levels of HMGB1, TNFalpha, IL-1beta, IL-10 and TGF-beta1 in the culture supernatants were measured by ELISA. Also, the mRNA expression for IL-10 and TGF-beta1 was assessed by RT-PCR. RESULTS LPS induced HMGB1 release at 8 h and reached a peak at 48 h. Significant (p < 0.05) production of TNFalpha, IL-1beta, IL-10, and TGF-beta1 was seen after 8 h. However, while the levels of TNFalpha and IL-beta remained elevated, IL-10 and TGF-beta1 release markedly declined by 24 h after stimulation. When cells were stimulated in the presence of conditioned medium derived from a 24 h LPS-stimulated culture, the production of TNFalpha and IL-1beta was increased while IL-10 and TGF-beta1 release and mRNA transcripts were decreased. A neutralizing anti-HMGB1 antibody added to the conditioned media reveresed these responses. CONCLUSIONS HMGB1 modulates the inflammatory cascade in activated macrophages by inducing proinflammatory, while suppressing anti-inflammatory responses.

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
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
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D016753	Interleukin-10	A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.	IL-10,CSIF-10,Cytokine Synthesis Inhibitory Factor,IL10,Interleukin 10
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus