Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation

Palumbo, Roberta; Gálvez, Beatriz G.; Pusterla, Tobias; Marchis, Francesco De; Cossu, Giulio; Marcu, Kenneth B.; Bianchi, Marco E.

doi:10.1084/jem20411oia24

Cited by 80 publications

(104 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results are in agreement with previous observations that indicate that mesoangioblasts migrate in response to the recombinant-purified HMGB1 and TNF-␣ signals (refs. [17,19], and see below). A recent study demonstrated that the proinflammatory activity of HMGB1 partially depends on its ability to bind to inflammatory cytokines [36].…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways

Lolmède

Campana

Vezzoli

et al. 2009

Journal of Leukocyte Biology

Self Cite

196

167

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

“…Mesoangioblasts have the property to cross endothelial barriers. Chemoattractants generated at the site of tissue injury, including high mobility group box 1 (HMGB1) and TNF-␣ [17][18][19], are likely to favor the homing of circulating progenitors to damaged tissues. The origin of these chemoattractants is still poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways

Lolmède

Campana

Vezzoli

et al. 2009

Journal of Leukocyte Biology

Self Cite

196

167

View full text Add to dashboard Cite

“…HMGB1 binds to the endogenous receptor for advanced glycation endproducts [7], exogenous toll-like receptor 2/4/9 (TLR2/4/9) [8,9], and CD24/Siglec-10 [10], and induces the expression of proinammatory cytokines, chemokines, and adhesion molecules [3,6]. Although, HMGB1 was initially thought to be a late mediator of sepsis, recent data also indicated that HMGB1 is associated with many other pathological conditions, such as autoimmune disease [11], cancer [12][13][14], trauma, ischemia-reperfusion injury [15,16], tissue repair and regeneration [17,18], and cardiovascular diseases [19]. Furthermore, HMGB1 has restorative effects on CD4 1 T-helper cell modulation [20].…”

Section: Introductionmentioning

confidence: 99%

“…thought to be a late mediator of sepsis, recent data also indicated that HMGB1 is associated with many other pathological conditions, such as autoimmune disease [11], cancer [12][13][14], trauma, ischemia-reperfusion injury [15,16], tissue repair and regeneration [17,18], and cardiovascular diseases [19]. Furthermore, HMGB1 has restorative effects on CD4 1 T-helper cell modulation [20].…”

mentioning

confidence: 99%

HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion

Sun

Zhou

et al. 2011

Eur J Immunol

View full text Add to dashboard Cite

High-mobility group box 1 (HMGB1), a non-histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3-triggered myocarditis and promoted by the post-infectious autoimmune process. Th17 cells, a novel CD4 1 T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti-HMGB1 B box mAb attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL-17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17-cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.Key words: Dilated cardiomyopathy . Experimental myocarditis . HMGB1 . Th17 cells IntroductionHigh-mobility group box 1 (HMGB1), a non-histone nuclear protein, has been functionally characterized as an alarmin or damage-associated molecular pattern (DAMP) [1,2]. It is constitutively expressed in quiescent cells and stored in the nucleus [3]. HMGB1 is one of the most evolutionarily conserved proteins in eukaryotes, with 100% identity between mice and rats, and 99% identity between rodents and humans [3].HMGB1 has been shown to be involved in both infectious and non-infectious inflammatory disease [2,4]. HMGB1 is released into the extracellular milieu during cell apoptosis/death [5], and by macrophages and monocytes in response to cellular stress or injury [6]. HMGB1 binds to the endogenous receptor for advanced glycation endproducts [7], exogenous toll-like receptor 2/4/9 (TLR2/4/9) [8,9], and CD24/Siglec-10 [10], and induces the expression of proinammatory cytokines, chemokines, and adhesion molecules [3,6]. Although, HMGB1 was initially 3586thought to be a late mediator of sepsis, recent data also indicated that HMGB1 is associated with many other pathological conditions, such as autoimmune disease [11], cancer [12][13][14], trauma, ischemia-reperfusion injury [15,16], tissue repair and regeneration [17,18], and cardiovascular diseases [19]. Furthermore, HMGB1 has restorative effects on CD4 1 T-helper cell modulation [20].Dilated cardiomyopathy (DCM) is one of the leading causes of severe heart failure and the most common indication for heart transplantation. DCM is often caused by coxsackievirus B3-triggered myocarditis [21]. Experimental autoimmune myocarditis (EAM) is a mouse model of postinfectious myocarditis, characterized by inflammatory infiltration of the myocardium and cardiac myocyte ne...

show abstract

“…[22][23][24][25] Here, we demonstrate that the efficacy of MABs cells to reconstitute dystrophic muscle is improved by the expression of the MAGE protein necdin. Importantly when necdin is overexpressed, both the myogenic differentiation and survival of MABs were enhanced both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 76%

Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation

et al. 2011

View full text Add to dashboard Cite

Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Vessel-associated stem cells, such as mesoangioblasts (MABs), appear to be the most promising cell type for the cell therapy for muscular dystrophies and have been shown to significantly contribute to restoration of muscle structure and function in different muscular dystrophy models. Here, we report that melanoma antigen-encoding gene (MAGE) protein necdin enhances muscle differentiation and regeneration by MABs. When necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy in reconstituting regenerating myofibres in the a-sarcoglycan dystrophic mouse. Moreover, necdin enhances survival when MABs are exposed to cytotoxic stimuli that mimic the inflammatory dystrophic environment. Taken together, these data demonstrate that overexpression of necdin may be a crucial tool to boost therapeutic applications of MABs in dystrophic muscle.

show abstract

Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation

Cited by 80 publications

References 1 publication

Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways

Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways

HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion

Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation

Contact Info

Product

Resources

About