High mobility group box 1 skews macrophage polarization and negatively influences phagocytosis of apoptotic cells

Schaper, Fleur; Leeuw, Karina de; Horst, G. A. Van Der; Bootsma, Hendrika; Limburg, Pieter C.; Heeringa, Peter; Bijl, Marc; Westra, Johanna

doi:10.1093/rheumatology/kew324

Cited by 60 publications

(53 citation statements)

References 42 publications

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“…Recent work showed that HMGB1 modulates the polarization of macrophages ( Schaper et al, 2016 ; Son et al, 2016 ). The switch from a proinflammatory to a tissue-healing phenotype in macrophages is an essential step in muscle regeneration to limit the inflammatory response and favor myogenesis ( Arnold et al, 2007 ; Cohen and Mosser, 2013 ; Saclier et al, 2013 ; Wang et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

High mobility group box 1 orchestrates tissue regeneration via CXCR4

Tirone

Tran

Ceriotti

et al. 2017

Journal of Experimental Medicine

121

155

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Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. Tirone et al. show that alternative redox forms of high mobility group box 1 (HMGB1), the “alarmin” signal released by damaged cells, trigger inflammation or tissue repair after injury by interacting with distinct receptors and that a nonoxidizable HMGB1 mutant promotes regeneration without exacerbating inflammation.

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Section: Resultsmentioning

confidence: 99%

High mobility group box 1 orchestrates tissue regeneration via CXCR4

Tirone

Tran

Ceriotti

et al. 2017

Journal of Experimental Medicine

121

155

View full text Add to dashboard Cite

show abstract

“…Then we compared the phenotype of monocytes between SLE patients and healthy donors. Although the M1 and M2 phenotypes were designed to define macrophages, the specific markers were conclusively expressed on monocytes 32 . Our results showed lower expression of CD14 + CD163 + (M2-like) in SLE monocytes, which is consistent with previous research, however, the previous study reported no difference in the expression of CD86 between patients and healthy donors 32 , but we found extremely higher expression of CD86 in the patients’ monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Although the M1 and M2 phenotypes were designed to define macrophages, the specific markers were conclusively expressed on monocytes 32 . Our results showed lower expression of CD14 + CD163 + (M2-like) in SLE monocytes, which is consistent with previous research, however, the previous study reported no difference in the expression of CD86 between patients and healthy donors 32 , but we found extremely higher expression of CD86 in the patients’ monocytes. We supposed the reason might be the patient inclusion criteria, to avoid drug effect as much as possible, our patients were all diagnosed for the first time, only 5 of them had accepted prednisolone treatment before and the therapy duration was strictly controlled within 7 days, however, in their study, most of the patients had accepted prednisolone, hydroxychloroquine, or immunosuppressive therapy, the multiple drugs may affect the final phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway

et al. 2018

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Alternatively activated macrophages have been reported to be helpful to alleviate systematic lupus erythematosus (SLE), and azithromycin could serve as an immunomodulator by promoting alternatively activated macrophage phenotype. However, the effect of azithromycin in SLE and the involved mechanism remain undetermined. The aim of this study is to characterize azithromycin and the underlying mechanism contributing to SLE therapy. First, we compared monocytes from SLE patients and matched healthy donors, and found monocytes from SLE patients exhibited more CD14+CD86+ cells, impaired phagocytic activity, and elevated interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α (the classical activated phenotype), which could be blocked by azithromycin. On the contrary, there were fewer CD14+CD163+ cells in SLE patients, accompanied by decreased arginase (Arg)-1 and found in inflammatory zone (Fizz)-1 (the alternatively activated phenotype). And IL-10, the crucial immune regulatory factor secreted by alternatively activated monocytes/macrophages, also showed a decreased trend in SLE patients. In addition, all these markers were up-regulated after azithromycin treatment. Next, we used activated lymphocyte-derived-DNA to imitate SLE macrophages in vitro to investigate the possible mechanism involved. Azithromycin showed the same effect in imitated SLE macrophages, with distinct Akt phosphorylation at 30 min and 12 h. After inhibiting Akt phosphorylation by LY294002, the down-regulation of CD80, IL-1β, IL-6, and TNF-α caused by azithromycin raised again, meanwhile, the up-regulation of CD206, Arg-1, Fizz-1, and IL-10 due to azithromycin was abolished. Additionally, insulin-like growth factor 1 (IGF-1), the specific agonist of Akt, played a similar role to azithromycin in imitated SLE macrophages. Taken together, our data indicated a novel role of azithromycin in alleviating SLE by promoting alternatively activated macrophage phenotype, and the PI3K/Akt signaling pathway was involved. Our findings provide a rationale for further investigation of novel therapeutic strategy for SLE patients.

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“…Most studies support dysfunctional and reduced phagocytosis in SLE patients, ultimately resulting in reduced clearance of apoptotic cells ( 56 – 58 ). Part of this phenotype may be regulated by UVB as HMGB1can skew macrophage polarization toward an M1-like phenotype diminishing their ability to phagocytose apoptotic cells ( 59 ).…”

Section: Introductionmentioning

confidence: 99%

Human and Murine Evidence for Mechanisms Driving Autoimmune Photosensitivity

et al. 2018

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Ultraviolet (UV) light is an important environmental trigger for systemic lupus erythematosus (SLE) patients, yet the mechanisms by which UV light impacts disease are not fully known. This review covers evidence in both human and murine systems for the impacts of UV light on DNA damage, apoptosis, autoantigen exposure, cytokine production, inflammatory cell recruitment, and systemic flare induction. In addition, the role of the circadian clock is discussed. Evidence is compared in healthy individuals and SLE patients as well as in wild-type and lupus-prone mice. Further research is needed into the effects of UV light on cutaneous and systemic immune responses to understand how to prevent UV-light mediated lupus flares.

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High mobility group box 1 skews macrophage polarization and negatively influences phagocytosis of apoptotic cells

Cited by 60 publications

References 42 publications

High mobility group box 1 orchestrates tissue regeneration via CXCR4

High mobility group box 1 orchestrates tissue regeneration via CXCR4

Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway

Human and Murine Evidence for Mechanisms Driving Autoimmune Photosensitivity

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