RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages
| Autor: | Ulf Andersson, R. Kokkola, B. Arnold, P. Nawroth, Helena Erlandsson Harris, Therese Östberg, Åsa Andersson, Carl Johan Treutiger, Robert A. Harris, G. Mullins |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Male medicine.medical_treatment Immunology Receptor for Advanced Glycation End Products chemical and pharmacologic phenomena Receptors Cell Surface Biology In Vitro Techniques HMGB1 Nitric Oxide RAGE (receptor) Proinflammatory cytokine Mice medicine Animals HMGB1 Protein Phosphorylation Receptors Immunologic Protein kinase A Receptor Extracellular Signal-Regulated MAP Kinases Mice Knockout Receptors Interleukin-1 Type I Tumor Necrosis Factor-alpha Macrophages High Mobility Group Proteins Histocompatibility Antigens Class II NF-kappa B Receptors Interleukin-1 hemic and immune systems General Medicine Macrophage Activation Molecular biology Recombinant Proteins Toll-Like Receptor 2 Rats Mice Inbred C57BL Repressor Proteins Cytokine biology.protein Cytokines Tumor necrosis factor alpha Female Inflammation Mediators |
| Zdroj: | Karolinska Institutet |
| ISSN: | 0300-9475 |
| Popis: | High-mobility group box chromosomal protein 1 (HMGB1) is a protein with both intranuclear functions and extracellular cytokine-like effects. In this report, we study possible candidate receptors for HMGB1 on macrophages (Mphi) and define pathways activated by HMGB1 binding. Bone marrow Mphi were prepared from Dark Agouti (DA) rats and stimulated in vitro with HMGB1. The kinetics of tumour necrosis factor (TNF) production, NO production, activation of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK- and SAPK/JNK-signalling pathways, nuclear translocation of nuclear factor kappa B (NF-kappaB) and HMGB1-induced upregulation of major histocompatibility complex (MHC) class II and CD86 were analysed. Mphi from interleukin (IL)-1 receptor type I-/-, Toll-like receptor 2 (TLR2-/-) and RAGE-/- mice were used to investigate the role of these receptors in HMGB1 signalling. HMGB1 induced TNF and NO production by Mphi, phosphorylation of all investigated MAP kinase pathways and NF-kappaB translocation, and expression of MHC class II was increased. Mphi from RAGE-/- mice produced significantly lower amounts of TNF, IL-1beta and IL-6, while IL-1RI-/- and TLR2-/- Mphi produced cytokine levels comparable with wildtype controls in response to HMGB1 stimulation. We conclude that HMGB1 has the potential to induce a proinflammatory phenotype in Mphi, with RAGE as the major activation-inducing receptor. |
| Databáze: | OpenAIRE |
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