High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina

Mohammad, Ghulam; Siddiquei, Mohammad Mairaj; Othman, Amira; Al‐Shabrawey, Mohamed; El‐Asrar, Ahmed M. Abu

doi:10.1016/j.exer.2012.12.009

Cited by 71 publications

(99 citation statements)

References 49 publications

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“…Generally, HMGB1 is expressed at a basal level as an architectural chromatin-binding protein, but at a slightly elevated level via passive release from damaged or necrotic cells (Beyer et al, 2012;Yi et al, 2013) or active secretion (Akirav et al, 2012;Kang et al, 2013;Mohammad et al, 2013). Moreover, overexpression of HMGB1 protein is observed in breast, colon, and gastrointestinal cancers, as well as in leukemia and other diseases (Kostova et al, 2010;Ohmori et al, 2011;Jube et al, 2012;Lee et al, 2012;Liu et al, 2012;Xing et al, 2012;Yu et al, 2012;Stoetzer et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In the nucleus, HMGB1 functions as a non-histone nucleosomal protein that binds DNA, contributes to stabilization of nucleosomes, and promotes DNA repair and replication (Bustin, 1999). In the extracellular milieu, HMGB1 is a pro-inflammatory cytokine that acts as an alarmin via passive release from damaged or necrotic cells (Beyer et al, 2012;He et al, 2012;Yi et al, 2013) or by active secretion from innate immune system cells in response to LPS, TNF-a or IL-1β stimulation to induce T-cell activation, cytokine production, and inflammatory responses by the transduction of cellular signals through its receptors (Akirav et al, 2012;Kang et al, 2013;Mohammad et al, 2013). Aside from these pro-inflammatory functions, HMGB1 protein also promotes regeneration processes and accelerates cell cycle progression.…”

Section: Introductionmentioning

confidence: 99%

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Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

Zhang

Wang²,

ZhiGuo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in Tax + -T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into Tax --T cells (TaxN, Jurkat) and Tax + -T cells (TaxP). We found that promoter activity in Tax + -T cells to be higher than that in Tax

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

Zhang

Wang²,

ZhiGuo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…In addition, we demonstrated increased levels of HMGB1 in the vitreous samples from patients with PDR and that there were significant positive correlations between the vitreous levels of HMGB1 and the levels of the inflammatory biomarkers [20][21][22]. Furthermore, we demonstrated that diabetes induced significant upregulation of the expression of HMGB1 and RAGE in the retinas of rats and mice and that intravitreal administration of HMGB1 to normal rats induced activation of inflammatory signaling pathways in the retina and increased retinal vascular permeability [21,23].…”

Section: Introductionmentioning

confidence: 76%

“…Sprague Dawley rats (200−220 g) were kept under deep anesthesia, and sterilized solution of recombinant HMGB1 (5 ng/5 L; R&D Systems, Minneapolis, MN) was injected into the vitreous of the right eye as previously described by us [23]. For the control, the left eye received 5 L of sterile phosphate buffer saline (PBS).…”

Section: Intravitreal Injection Of Hmgb1mentioning

confidence: 99%

The proinflammatory cytokine high‐mobility group box‐1 mediates retinal neuropathy induced by diabetes

Asrar¹,

Siddiquei²,

Nawaz³

et al. 2014

Acta Ophthalmologica

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To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1) in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2), cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.

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“…18 Within the retina, it has been reported that HMGB-1 expression is observed during diabetic and uveitic retinopathies. 19,20 We have previously reported that the expression of HMGB-1 in the retina is higher in glaucomatous than in normotensive rats. 21 However, the exact role of and the mechanisms underlying HMGB-1 activity under high-pressure conditions remain to be elucidated.…”

mentioning

confidence: 99%

The pro-inflammatory role of high-mobility group box 1 protein (HMGB-1) in photoreceptors and retinal explants exposed to elevated pressure

Böhm

Schallenberg

Brockhaus

et al. 2016

Laboratory Investigation

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To determine the role of high-mobility group box 1 protein (HMGB-1) in cellular and tissue models of elevated pressureinduced neurodegeneration, regeneration, and inflammation. Mouse retinal photoreceptor-derived cells (661W) and retinal explants were incubated either under elevated pressure or in the presence of recombinant HMGB-1 (rHMGB-1) to investigate the mechanisms of response of photoreceptors. Immunohistochemistry, western blotting, and the quantitative real-time PCR were used to examine the expression levels of immunological factors (eg, HMGB-1, receptor for advanced glycation end products (RAGE)), Toll-like receptors 2 and 4 (TLR-2, TLR-4), apoptosis-related factors (eg, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad)) as well as cytokine expression (eg, tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-6, and vascular endothelial growth factor (VEGF)). The data revealed increased the expression of HMGB-1 and its receptors RAGE, TLR-2, and TLR-4, and TNF-α as well as pro-apoptotic factors (eg, Bad) as well as apoptosis in 661W cells exposed to elevated pressure. Co-cultivation of 661W cells with rHMGB-1 increased the expression levels of pro-apoptotic Bad and cleaved Caspase-3 resulting in apoptosis. Cytokine array studies revealed an increased release of TNF-α, IL-4, IL-6, and VEGF after incubation of 661W cells with rHMGB-1. Upregulation of HMGB-1, TLR-2, and RAGE as well as anti-apoptotic Bcl-2 expression levels was found in the retinal explants exposed to rHMGB-1 or elevated pressure. The results suggest that HMGB-1 promotes an inflammatory response and mediates apoptosis in the pathology of photoreceptors and retinal homeostasis. HMGB-1 may have a key role in ongoing damage of retinal cells under conditions of elevated intraocular pressure.

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High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina

Cited by 71 publications

References 49 publications

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

The proinflammatory cytokine high‐mobility group box‐1 mediates retinal neuropathy induced by diabetes

The pro-inflammatory role of high-mobility group box 1 protein (HMGB-1) in photoreceptors and retinal explants exposed to elevated pressure

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