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HMGB1 Products Available by Family |
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Linear Diagram of High Mobility Group Box 1 Protein
IMG-6738 IMG-6740
IMG-6739 IMG-6655
IMG-6666
IMGENEX offers monoclonal and polyclonal antibodies specific to the A-box and B-box domains of HMGB1.
HMGB1: A Pro-Inflammatory Alarmin Family Member
High mobility group box 1 (HMGB1) is a key member of the alarmin family. HMGB1 had previously been characterized as a ubiquitous, non-histone architectural chromosomal protein but is now classified as a cytokine with a central role in inflammatory processes1,2. HMGB1 is secreted in response to infection and tissue damage by necrotic and inflammatory effector cells such as monocytes and as a pro-inflammatory cytokine is capable of mediating tissue repair and angiogenesis. HMGB1 also has a direct and potent bactericidal activity3. Released as a late mediator during inflammation, HMGB1 participates in the pathogenesis of systemic inflammation after the initial mediator response has resolved. Therefore HMGB1 occupies a critical role as a pro-inflammatory mediator passively released by necrotic cells4 . During traumatic hemorrhage HMGB1 induces sterile inflammation via activation of TLR45. Triggering and activation of NF-kappaB- dependent transcription is also induced by HMGB1 via TLR4 and TLR2 but not via another HMGB1 receptor RAGE (receptor for advanced glycation end-products)6. However, through RAGE, HMGB1 induces inflammatory responses as well7. Taken together, HMGB1 is an important player in the innate immune defense armamentarium, but as a chemoattractant for dendritic cells HMGB1 can drive polarization of Th1 responses.TLR4 and TLR2 appear to be primary receptors of HMGB1, and other receptors, in addition to RAGE, have also been identified1,8. As a multifunctional protein HMGB1 has clear intracellular and extracellular functions and appears to be centrally involved in many inflammatory processes- a profile making it’s cell-associated detection and extracellular quantitation valuable indicators for more in depth analysis in normal immune responses or in pathogenic autoimmune inflammatory responses.
Related areas of study: HMGB1 Antibodies, Toll-like Receptors, Inflammation, Innate Immunity, NF-kB Pathway
HMGB1 Multi-Functional Intracellular and Extracellular Pro-Inflammatory Pathway Regulator
HMGB1 is a multi-functional regulator. Intracellularly it serves as a DNA binging protein causing DNA bending and facilitates binding of regulatory complexes to DNA like nuclear hormone receptors or V(D)J complexes. It can be released from necrotic cells directly or transported from activated immune cells in acetylated form from the nucleus of macrophages or dendritic cells through secretory lysosomes. HMGB1 can bind to soluble RAGE or through cell-bound RAGE or TLR2 or TLR4 and can activate the expression and release of other pro-inflammatory mediators and itself through a positive feedback loop through NF-kB signaling pathways. As depicted, among other activities HMGB1 can induce cell migration, enhances angiogenesis and promote tumor metastases.
References:
1. Oppenheim, J. J. & D. Yang (2005) Curr. Opin. Immunol. 17:359.
2. Andersson U, et al. ( 2002) J Leukoc Biol. 72:1084-91.
3. Zetterstrom, C. K. et al. (2003) Pediatr. Res. 52:148
4. Yamada Y et al. (2011) Arch Biochem Biophys. 506(2):188-93.
5. Cohen M.J. et al. 2009 Crit Care.13:R174.
6. Park JS et al. 2006 Am J Physiol Cell Physiol. 290:C917-24
7. Dubicke A, et al.. 2010 J Reprod Immunol. 84:86-94.
8. Yu, M. et al. (2006) Shock 26:174. |
