RGD Reference Report - High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. - Rat Genome Database

RGD Reference Report - High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. - Rat Genome Database

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General

High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes.
Authors:	Andersson, U Wang, H Palmblad, K Aveberger, AC Bloom, O Erlandsson-Harris, H Janson, A Kokkola, R Zhang, M Yang, H Tracey, KJ
Citation:	Andersson U, etal., J Exp Med. 2000 Aug 21;192(4):565-70.
RGD ID:	10054071
Pubmed:	PMID:10952726 (View Abstract at PubMed)
PMCID:	PMC2193240 (View Article at PubMed Central)
Lipopolysaccharide (LPS) is lethal to animals because it activates cytokine release, causing septic shock and tissue injury. Early proinflammatory cytokines (e.g., tumor necrosis factor [TNF] and interleukin [IL]-1) released within the first few hours of endotoxemia stimulate mediator cascades that persist for days and can lead to death. High mobility group 1 protein (HMG-1), a ubiquitous DNA-binding protein, was recently identified as a "late" mediator of endotoxin lethality. Anti-HMG-1 antibodies neutralized the delayed increase in serum HMG-1, and protected against endotoxin lethality, even when passive immunization was delayed until after the early cytokine response. Here we examined whether HMG-1 might stimulate cytokine synthesis in human peripheral blood mononuclear cell cultures. Addition of purified recombinant HMG-1 to human monocyte cultures significantly stimulated the release of TNF, IL-1alpha, IL-1beta, IL-1RA, IL-6, IL-8, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta; but not IL-10 or IL-12. HMG-1 concentrations that activated monocytes were within the pathological range previously observed in endotoxemic animals, and in serum obtained from septic patients. HMG-1 failed to stimulate cytokine release in lymphocytes, indicating that cellular stimulation was specific. Cytokine release after HMG-1 stimulation was delayed and biphasic compared with LPS stimulation. Computer-assisted image analysis demonstrated that peak intensity of HMG-1-induced cellular TNF staining was comparable to that observed after maximal stimulation with LPS. Administration of HMG-1 to Balb/c mice significantly increased serum TNF levels in vivo. Together, these results indicate that, like other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1), extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine synthesis.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of interleukin-1 production	involved_in	IDA		10054071	PMID:10952726	UniProt
positive regulation of interleukin-6 production	involved_in	IDA		10054071	PMID:10952726	UniProt
positive regulation of interleukin-8 production	involved_in	IDA		10054071	PMID:10952726	UniProt
positive regulation of macrophage inflammatory protein 1 alpha production	involved_in	IDA		10054071	PMID:10952726	UniProt
positive regulation of tumor necrosis factor production	involved_in	IDA		10054071	PMID:10952726	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Hmgb1 (high mobility group box 1)

Additional Information