High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE)

Abdulahad, Deena A.; Westra, Johanna; Reefman, Esther; Zuidersma, Erica; Bijzet, Johan; Limburg, Pieter C.; Kallenberg, Cees G. M.; Bijl, Marc

doi:10.1177/0961203313483377

Cited by 26 publications

(21 citation statements)

References 32 publications

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“…Melinda Magna 1 and David S Pisetsky of characteristic tissue pathology (for example, arthritis) or functional disturbance (for example, muscle weakness in myositis) by HMGB1 in in vitro or in vivo models; and (d) effectiveness of agents directed at HMGB1 in animal models (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Table 1 lists diseases in which studies implicate a role of HMGB1 in pathogenesis.…”

Section: The Role Of Hmgb1 In the Pathogenesis Of Inflammatory And Aumentioning

confidence: 99%

The Role of HMGB1 in the Pathogenesis of Inflammatory and Autoimmune Diseases

Magna

Pisetsky

2014

Mol Med

296

199

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High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory and autoimmune diseases once it is in an extracellular location. This translocation can occur with immune cell activation as well as cell death, with the conditions for release associated with the expression of different isoforms. These isoforms result from posttranslational modifications, with the redox states of three cysteines at positions 23, 45 and 106 critical for activity. Depending on the redox states of these residues, HMGB1 can induce cytokine production via toll-like receptor 4 (TLR4) or promote chemotaxis by binding the chemokine CXCL12 for stimulation via CXCR4. Fully oxidized HMGB1 is inactive. During the course of inflammatory disease, HMGB1 can therefore play a dynamic role depending on its redox state. As a mechanism to generate alarmins, cell death is an important source of HMGB1, although each major cell death form (necrosis, apoptosis, pyroptosis and NETosis) can lead to different isoforms of HMGB1 and variable levels of association of HMGB1 with nucleosomes. The association of HMGB1 with nucleosomes may contribute to the pathogenesis of systemic lupus erythematosus by producing nuclear material whose immunological properties are enhanced by the presence of an alarmin. Since HMGB1 levels in blood or tissue are elevated in many inflammatory and autoimmune diseases, this molecule can serve as a unique biomarker as well as represent a target of novel therapies to block its various activities.

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Section: The Role Of Hmgb1 In the Pathogenesis Of Inflammatory And Aumentioning

confidence: 99%

The Role of HMGB1 in the Pathogenesis of Inflammatory and Autoimmune Diseases

Magna

Pisetsky

2014

Mol Med

296

199

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“…HMGB1 can be passively released by necrotic or damaged cells [13] and can be detected in serum samples as a biomarker [14,15]. SSE can lead to HMGB1 release from injured cells into blood circulation [16], and cytoplasmic translocation has been detected in lung tissues from SSE-exposed rats [17] release is increased in the skin of SLE patients compared to healthy controls, and HMGB1 release contributes to the development of inflammatory skin lesions [18]. Ultraviolet (UV) irradiation induces an inflammatory skin response that is initiated by HMGB1 release from UV-damaged keratinocytes [19].…”

Section: Introductionmentioning

confidence: 99%

Secondhand smoke exposure-induced nucleocytoplasmic shuttling of HMGB1 in a rat premature skin aging model

Chaichalotornkul¹,

Nararatwanchai²,

Narkpinit³

et al. 2015

Biochemical and Biophysical Research Communications

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Secondhand cigarette smoke exposure (SSE) has been linked to carcinogenic, oxidative, and inflammatory reactions. Herein, we investigated whether premature skin aging could be induced by SSE in a rat model, and assessed the cytoplasmic translocation of high mobility group box 1 (HMGB1) protein and collagen loss in skin tissues. Animals were divided into two groups: SSE and controls. Whole body SSE was carried out for 12 weeks. Dorsal skin tissue specimens were harvested for HMGB1 and Mallory's azan staining. Correlations between serum HMGB1 and collagen levels were determined. Rat skin exposed to secondhand smoke lost collagen bundles in the papillary dermis and collagen decreased significantly (p<0.05) compared with control rats. In epidermal keratinocytes, cytoplasmic HMGB1 staining was more diffuse and there were more HMGB1-positive cells after four weeks in SSE compared to control rats. A negative correlation between HMGB1 serum and collagen levels (r=-0.631, p=0.28) was also observed. Therefore, cytoplasmic HMGB1 expression in skin tissues might be associated with skin collagen loss upon the initiation of SSE. Additionally, long-term SSE might affect the appearance of the skin, or could accelerate the skin aging process.

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“…Nucleosomes containing HMGB1, detected in the serum of SLE patients, led to production of inflammatory cytokines IL-6, IL1β, and TNF-α coupled to DC activation in a TLR-2 dependent manner (43). SLE patients with inflammatory skin lesions release HMGB1 at the lesion site upon exposure to UVB exposure (44). As a whole, reports show that HMGB1 is considered a potent inflammatory mediator in acute settings when associated with autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

Deletion of CD24 Impairs Development of Heat Shock Protein gp96–Driven Autoimmune Disease through Expansion of Myeloid-Derived Suppressor Cells

Thaxton

Liu

Zheng

et al. 2014

The Journal of Immunology

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CD24 binds to and suppresses inflammation triggered by danger associated molecular patterns (DAMPS) such as heat-shock proteins (HSPs) and HMGB1. Paradoxically, CD24 has been shown to enhance autoimmune disease. Here we attempt to reconcile this paradox by deletion of CD24 (24KO) in a lupus-like disease model driven by forced expression of HSP gp96 at the cell surface (tm). As expected, tm24KO mice showed increased CD11c+ DC activation coupled to a significant increase in DC-specific IL-12 production compared to tm mice. However, tm24KO mice showed less CD4 T cell activation and peripheral inflammatory cytokine production in comparison to tm mice. We characterized an enhanced immune suppressive milieu in tm24KO mice distinguished by increased TGF-β and greater Treg suppressive capacity. We found greater absolute numbers of MDSCs in tm24KO mice and showed that the Ly6C+ MDSC subset had greater suppressive capacity from tm24KO mice. Deletion of CD24 in tm mice led to diminished lupus-like pathology as evidenced by anti-nuclear antibody deposition and glomerulonephritis. Finally, we show that expanded MDSC populations were mediated by increased free HMGB1 in tm24KO mice. Thus, the deletion of CD24 in an HSP-driven model of autoimmunity led to the unexpected development of Treg and MDSC populations that augmented immune tolerance. Further study of these populations as possible negative regulators of inflammation in the context of autoimmunity is warranted.

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High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE)

Cited by 26 publications

References 32 publications

The Role of HMGB1 in the Pathogenesis of Inflammatory and Autoimmune Diseases

The Role of HMGB1 in the Pathogenesis of Inflammatory and Autoimmune Diseases

Secondhand smoke exposure-induced nucleocytoplasmic shuttling of HMGB1 in a rat premature skin aging model

Deletion of CD24 Impairs Development of Heat Shock Protein gp96–Driven Autoimmune Disease through Expansion of Myeloid-Derived Suppressor Cells

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