Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis

Li, Xiaoyun; Yan, Ye; Zhu, Yuanyuan; Xiong, Sidong

doi:10.1016/j.molimm.2015.01.023

Cited by 42 publications

(48 citation statements)

References 45 publications

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“…Lupus marked with irregular immune reactions which released suddenly if the triggering factors come. 30,31 The KP treatment in all doses gives many beneficial outcomes in the kidney to reduce and inhibit the glomerular swelling. It followed by the lower proteinuria level.…”

Section: Discussionmentioning

confidence: 99%

Repairing Effects of Aqueous Extract of Kalanchoe pinnata (Lmk) Pers. on Lupus Nephritis Mice

Indriyanti¹,

Garmana²,

Setiawan³

2018

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Kalanchoe pinnata (Lmk) Pers (KP) has an immunosuppressive effect on delayed-type hypersensitivity test. Based on it, this research aimed to determine the repairing effects of aqueous extract of KP on lupus nephritis mice and identified its active compound. The KP extract profile was determined using UPLC-QTOF-MS/MS instrument. We examined six mice groups consisting of three curative treatment groups, one standard group receiving prednisone, one preventive group receiving KP extract, and one healthy (healthy and untreated) group. At the end of the experiment, we measured the proteinuria and renal histology parameters. To recognize the active compound in the KP profile, we performed in silico assays for the flavonoid compounds to bind to the glucocorticoid receptor. We played in silico tests for the flavonoid compounds to identify the active compound in the KP profile. We found the repairing effect of KP was detected in the kidney, demonstrated by its low proteinuria level and its better tissue structure. In the curative group, the urine protein level and its glomerular inflammation decreased. In the preventive group, the aqueous extract of KP could prevent lupus nephritis manifestations in the kidney. Bryophyllin A is the most active compound of the KP. However, further research is needed to understand the mechanism involved. We conclude, the aqueous extract, especially its bryophyllin A, have beneficial effects in repairing the function and tissue structure of lupus manifestations in mice kidney.

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Section: Discussionmentioning

confidence: 99%

Repairing Effects of Aqueous Extract of Kalanchoe pinnata (Lmk) Pers. on Lupus Nephritis Mice

Indriyanti¹,

Garmana²,

Setiawan³

2018

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“…In addition, Li et al recently reported that blocking serum HMGB1 with glycyrrhizin, a traditional herbal medicine that blocks HMGB1, alleviated lupus nephritis induced in mice by activated lymphocyte-derived DNA (ALD-DNA) (33). In this model, lupus nephritis is induced by active immunization of mice with DNA from lymphocytes that have undergone activation-induced cell death (ALD-DNA) in complete Freund's adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…In the disease models described by Li et al and Zhang et al, which do show a positive effect of blocking HMGB1, it is unclear whether anti-HMGB1 antibodies are also present (33,36). At present, the role of endogenously formed anti-HMGB1 antibodies in disease pathogenesis is unclear and warrants further investigation.…”

mentioning

confidence: 92%

Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

Schaper

Timmeren

Petersen

et al. 2016

Mol Med

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High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 μg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti-HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice.

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“…10,11 When bound to the Receptor for Advanced Glycation Endproducts (RAGE), it facilitates the transport of RNA and DNA to endosomal TLRs, leading to the production of type 1 interferon (IFN), IFN-inducible genes, and proinflammatory cytokines, which skew the differentiation of monocytes toward proinflammatory macrophages. 9,[12][13][14][15] Significantly elevated serum levels of HMGB1 have been demonstrated in SLE patients, 16,17 and administration of antibodies against HMGB1 confer protection against tissue injury in some experimental models of autoimmune disease and inflammation. 18 HMGB1 has also been shown to suppress inflammation.…”

Section: Introductionmentioning

confidence: 99%

C1q and HMGB1 reciprocally regulate human macrophage polarization

Son

Porat

et al. 2016

Blood

143

121

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Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis

Cited by 42 publications

References 45 publications

Repairing Effects of Aqueous Extract of Kalanchoe pinnata (Lmk) Pers. on Lupus Nephritis Mice

Repairing Effects of Aqueous Extract of Kalanchoe pinnata (Lmk) Pers. on Lupus Nephritis Mice

Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

C1q and HMGB1 reciprocally regulate human macrophage polarization

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