No abstract available.
HMGB1 Protein* ; Pemphigus*

Humans ; Asthma/diagnosis* ; HMGB1 Protein

HMGB1 is a widely existing DNA-binding nuclear protein, participating in gene transcription, damage repair, recombination and stabilizing nucleosome construction. Under injury, infection and chemotherapy, HMGB1 can be released by nature immunocyte and necrosis cells as a DAMP, exerting pleiotropic biological effects by binding to RAGE, TLR and CXCL12, which lead to activation of CDC42, mitogen-activated protein kinases (MAPKs), c-IAP and NF-κB, thereby promoting angiogenesis, unlimited replicative potential, tissue invasion and metastasis. And it also involves in immune response by regulating immunocyte function as a immunocyte warning signal. Scholars have detected that HMGB1 is over expressed and released following chemotherapy and radiation therapy in cells of hematological malignancies, promoting malignant cell replication, decreasing therapeutic effect. Recently, endogenous HMGB1 has been implied to be an intrinsic modulator of autophagy and referenced to resistant to apoptosis in malignant hematosis cells. In contrast, through suppression of HMGB1 expression, tumor cell apoptosis and chemotherapeutic drug sensitivity were increased, which will be a new strategy for the treatment of hematological malignancies. In this article, the basic characteristics of HMGB1, including structure and biological features, and HMGB1 and tumors such as lymphoma, myeloproliferative neoplasms and acute myeloid leukemia are reviewed.
Animals ; HMGB1 Protein ; Hematologic Neoplasms ; therapy ; Humans

High mobility group box-1 protein (HMGB1), which is a nuclear protein, participates in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury. In the initial stage of injury, there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens, but this pro-inflammatory period is transient, and it is followed by a prolonged period of immune suppression. At present, several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity, which may enhance the production of early proinflammatory mediators, and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity. The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation, however, this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.
Cytokines ; immunology ; HMGB1 Protein ; immunology ; Humans ; Immunity, Cellular ; Inflammation ; immunology

Endotoxemia ; metabolism ; pathology ; HMGB1 Protein ; Humans ; Liver ; metabolism ; pathology

Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of asthma. The supernatant of the eosinophil culture was found to significantly increase the levels of interleukin (IL)-4 and IL-5 in the supernatant of CD4+ T cells co-cultured with DCs. HMGB1 levels increased in the supernatant of the eosinophil culture stimulated with IL-5. Anti-HMGB1 antibodies significantly attenuated increases of IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with DCs that were induced by the supernatant of the eosinophil culture. In addition, anti-HMGB1 antibodies significantly attenuated the expressions of activation markers (CD44 and CD69) on CD4+ T cells. Our data suggest that eosinophils modulate CD4+ T cell responses via HMGB1 in the pathogenesis of asthma.
Antibodies ; Asthma* ; Dendritic Cells ; Eosinophils* ; HMGB1 Protein ; Inflammation ; Interleukin-4 ; Interleukin-5 ; Interleukins ; T-Lymphocytes

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the postischemic brain, HMGB1 is massively released during NMDA-induced acute damage and triggers inflammatory processes. In a previous study, we demonstrated that intranasally delivered HMGB1 binding heptamer peptide (HBHP; HMSKPVQ) affords robust neuroprotective effects in the ischemic brain after middle cerebral artery occlusion (MCAO, 60 minutes). In the present study, we investigated HBHP-induced anti-inflammatory effects on microglia activation. In LPS-treated primary microglia culture, HMGB1 was rapidly released and accumulated in culture media. Furthermore, LPS-conditioned media collected from primary microglia cultures (LCM) activated naive microglia and markedly induced NO and proinflammatory cytokines. However, the suppression of HMGB1 by siRNA-HMGB1, HMGB1 A box, or anti-HMGB1 antibody significantly attenuated LCM-induced microglial activation, suggesting that HMGB1 plays a critical role in this process. A pull-down assay using biotin-labeled HBHP showed that HBHP binds directly to HMGB1 (more specifically to HMGB1 A box) in LCM. In addition, HBHP consistently inhibited LCM-induced microglial activation and suppressed the inductions of iNOS and proinflammatory cytokines. Together these results suggest that HBHP confers anti-inflammatory effects in activated microglia cultures by forming a complex with HMGB1.
Brain ; Culture Media ; Cytokines ; HMGB1 Protein ; Infarction, Middle Cerebral Artery ; Inflammation ; Microglia* ; Neuroprotective Agents

High mobility group box 1 protein (HMGB1), a damage-associated molecular pattern, exists ubiquitously in the cells of mammals. It contributes to maintaining the structure of nucleosome and modulating transcription of gene in nuclei. Extracellular HMGB1 plays two-way roles in promoting inflammatory and tissue repair. Released actively as well as passively following cytokine stimulation during cell death, HMGB1 may act as a late inflammatory factor and an endogenous damage-associated molecular pattern recognized by its receptors. And it may mediate the occurrence, development and outcome of the inflammatory injury of digestive system diseases, such as gastric mucosal injury, inflammatory bowel-disease, liver injury, pancreatitis, and so on. This review mainly concerns the research progresses of HMGB1 in the inflammatory injury of digestive system diseases. At the same time, HMGB1 itself, or as a therapeutic target, can promote tissue repair.
Animals ; Digestive System Diseases ; pathology ; HMGB1 Protein ; metabolism ; Humans ; Inflammation ; pathology

Animals ; Endotoxins ; Female ; HMGB1 Protein ; biosynthesis ; Liver Failure, Acute ; chemically induced ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the association between serum level of high-mobility group box 1(HMGB1) and neonatal respiratory distress syndrome (NRDS).

METHODSA total of 35 infants with NRDS and 35 normal neonates (control group) were enrolled. Peripheral venous blood samples were collected with 12-24 hours after birth. ELISA was used to measure the serum level of HMGB1.

RESULTSThe infants with mild and severe NRDS had a significantly higher serum level of HMGB1 than the control group (P<0.05). The infants with severe NRDS had a significantly higher serum level of HMGB1 than those with mild NRDS (P<0.05). The infants with NRDS who died had a significantly higher serum level of HMGB1 than those who survived (P<0.05). The receiver operating characteristic (ROC) curve showed that the optimal cut-off value for serum level of HMGB1 to predict NRDS was 625.3 pg/mL with an area under the ROC curve (AUC) of 0.846 (95%CI: 0.755-0.936), and the optimal cut-off value for serum level of HMGB1 to predict the death of infants with NRDS was 772.2 pg/mL with an AUC of 0.916 (95%CI: 0.813-1.000).

CONCLUSIONSInfants with NRDS have a significant increase in the serum level of HMGB1, and the serum level of HMGB1 can well predict the development and prognosis of NRDS.

Female ; HMGB1 Protein ; blood ; Humans ; Infant, Newborn ; Male ; Prognosis ; Respiratory Distress Syndrome, Newborn ; blood ; diagnosis