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High mobility group...
High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes
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- Andersson, U (author)
- Karolinska Institutet
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Wang, HC (author)
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- Palmblad, K (author)
- Karolinska Institutet
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- Aveberger, AC (author)
- Karolinska Institutet
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Bloom, O (author)
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- Erlandsson-Harris, H (author)
- Karolinska Institutet
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Janson, A (author)
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Kokkola, R (author)
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Zhang, MH (author)
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Yang, H (author)
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Tracey, KJ (author)
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(creator_code:org_t)
- 2000-08-21
- 2000
- English.
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 192:4, s. 565-570
- Related links:
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http://jem.rupress.o...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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-1α, IL-1β, IL-1RA, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and MIP-1β; 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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- By the author/editor
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Andersson, U
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Wang, HC
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Palmblad, K
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Aveberger, AC
-
Bloom, O
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Erlandsson-Harri ...
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show more...
-
Janson, A
-
Kokkola, R
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Zhang, MH
-
Yang, H
-
Tracey, KJ
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show less...
- Articles in the publication
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The Journal of e ...
- By the university
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Karolinska Institutet