| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Andersson, U, et al.
(författare)
-
High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes
- 2000
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 192:4, s. 565-570
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 6. |
- Andersson, U, et al.
(författare)
-
HMGB1 as a DNA-binding cytokine
- 2002
-
Ingår i: Journal of leukocyte biology. - 0741-5400. ; 72:6, s. 1084-1091
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Andersson, U, et al.
(författare)
-
HMGB1 is a potent trigger of arthritis
- 2004
-
Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 344-350
-
Tidskriftsartikel (refereegranskat)
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Aulin, C., et al.
(författare)
-
The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury
- 2022
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 30:9, s. 1198-1209
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation. Methods: HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed. Results: The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines. Conclusions: HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Larsson, E, et al.
(författare)
-
Serum concentrations of cartilage oligomeric matrix protein, fibrinogen and hyaluronan distinguish inflammation and cartilage destruction in experimental arthritis in rats.
- 2002
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1460-2172 .- 1462-0324. ; 41, s. 996-
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:We investigated if changes in serum/plasma fibrinogen (FIB), hyaluronan (HA) and cartilage oligomeric matrix protein (COMP) levels can be used to differentiate between inflammation and cartilage involvement during arthritis. METHODS:Collagen-induced arthritis (CIA), oil-induced arthritis (OIA) and for comparison, experimental autoimmune encephalitis (EAE) induced in DA rats were investigated. RESULTS:Elevations of FIB concentrations were apparent at days 4-7 post-immunization in both arthritis models reaching a maximum on day 20-21, i.e. before peak arthritis. Elevations of HA in both models were seen shortly before macroscopically apparent arthritis, and peaked at or just before maximal arthritis, i.e. later in CIA than in OIA. COMP levels increased only after onset of arthritis and peaked late in disease (days 34-37), being significantly higher in the more destructive CIA compared with the less destructive OIA. During EAE flares, only FIB levels increased. CONCLUSIONS:FIB is a general inflammation marker, HA appears to be a marker for synovitis and changes in COMP levels appear to reflect the cartilage destruction process.
|
|
| 28. |
|
|
| 29. |
- Lundberg, K., et al.
(författare)
-
A pH-induced modification of CII increases its arthritogenic properties
- 2004
-
Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 23:2, s. 95-102
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoreactivity to collagen type II (CII) has been implicated in the pathogenesis of rheumatoid arthritis. Patients have been described to have an acidic pH in their inflamed synovial tissue. It is known that protein structures are modified by environmental pH, thus it is plausible that changes in synovial pH could affect the conformation of proteins like CII. Posttranslational modifications could alter the biophysical properties of cartilage proteins leading to autoimmunity. In this study we investigated if arthritogenicity of CII was affected by changes in pH, and if so, this could be correlated to altered protein conformation. Immunisation with CII at neutral pH induced a milder disease than did CII at acidic pH. All animals elicited a humoral response to CII, although with a significantly higher IgG1/IgG2b-ratio in the pH 7.4 group. Analysis by circular dichroism and electron microscopy indicated less fibrillation of CII at low pH as compared to neutral pH. Our results suggest that CII is more immunogenic and arthritogenic in an acidic environment than in a neutral environment. We can correlate these findings to pH-induced conformational changes of CII. Hence, self-tolerance to CII might be affected by changes in pH leading to altered and increased arthritogenicity. © 2004 Elsevier Ltd. All rights reserved.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
- Yang, HA, et al.
(författare)
-
A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release
- 2010
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 107:26, s. 11942-11947
-
Tidskriftsartikel (refereegranskat)abstract
- During infection, vertebrates develop “sickness syndrome,” characterized by fever, anorexia, behavioral withdrawal, acute-phase protein responses, and inflammation. These pathophysiological responses are mediated by cytokines, including TNF and IL-1, released during the innate immune response to invasion. Even in the absence of infection, qualitatively similar physiological syndromes occur following sterile injury, ischemia reperfusion, crush injury, and autoimmune-mediated tissue damage. Recent advances implicate high-mobility group box 1 (HMGB1), a nuclear protein with inflammatory cytokine activities, in stimulating cytokine release. HMGB1 is passively released during cell injury and necrosis, or actively secreted during immune cell activation, positioning it at the intersection of sterile and infection-associated inflammation. To date, eight candidate receptors have been implicated in mediating the biological responses to HMGB1, but the mechanism of HMGB1-dependent cytokine release is unknown. Here we show that Toll-like receptor 4 (TLR4), a pivotal receptor for activation of innate immunity and cytokine release, is required for HMGB1-dependent activation of macrophage TNF release. Surface plasmon resonance studies indicate that HMGB1 binds specifically to TLR4, and that this binding requires a cysteine in position 106. A wholly synthetic 20-mer peptide containing cysteine 106 from within the cytokine-stimulating B box mediates TLR4-dependent activation of macrophage TNF release. Inhibition of TLR4 binding with neutralizing anti-HMGB1 mAb or by mutating cysteine 106 prevents HMGB1 activation of cytokine release. These results have implications for rationale, design, and development of experimental therapeutics for use in sterile and infectious inflammation.
|
|
