Pathogenic Tconvs promote inflammatory macrophage polarization through GM‐CSF and exacerbate abdominal aortic aneurysm formation

Li, Dan; Li, Jingyong; Liu, Henan; Zhai, Luna; Hu, Wangling; Xia, Ni; Tang, Tingting; Jiao, Jiao; Lv, Bingjie; Nie, Shaofang; Hu, Desheng; Liao, Yuhua; Yang, Xun; Shi, Guo‐Ping; Cheng, Xiang

doi:10.1096/fj.202101576r

Cited by 6 publications

(4 citation statements)

References 60 publications

(111 reference statements)

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“…Macrophages are immune cells that play the role of “scavengers” and participate in various cellular and molecular immune pathways [ 23 ]. Macrophages also participate in the occurrence and development of many diseases such as sepsis [ 24 ], abdominal aortic aneurysm [ 25 ], endometriosis [ 26 ], brain injury [ 27 ], oral squamous cell carcinoma [ 28 ], liver fibrosis [ 15 ], liver cancer [ 29 ], and pancreatic cancer [ 30 ]. In recent years, long noncoding RNAs (lncRNAs) have become key molecules in the study of many diseases, and several studies on long noncoding RNAs related to the pathogenesis of macrophage polarization have been reported.…”

Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Liao

Ruan

Chen

et al. 2023

Mediators of Inflammation

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Macrophages are a type of immune cells with high levels of plasticity and heterogeneity. They can polarize into M1 or M2 functional phenotypes. These two phenotypes exhibit a dynamic balance during polarization-related diseases and play opposing roles. Long noncoding RNAs (lncRNAs) play an important role in biological processes such as cell proliferation, death, and differentiation; however, how long noncoding RNAs affect the cellular functionality of macrophages remains to be studied. Long noncoding RNA Gm9866 was found to be closely related to macrophage polarization through bioinformatics analysis. In this study, by conducting real-time polymerase chain reaction analysis, it was observed that long noncoding RNA Gm9866 expression significantly increased after treatment with interleukin-4 but significantly decreased after treatment with lipopolysaccharide. Fluorescence in situ hybridization revealed that long noncoding RNA Gm9866 was expressed mainly in the nucleus. Real-time polymerase chain reaction analysis showed that overexpression of long noncoding RNA Gm9866 in RAW264.7 cells further promoted the expression of M2 markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2). Western blotting analysis demonstrated inhibition of nuclear factor-κB (NF-κB) expression. EdU (5-ethynyl-2 ′ -deoxyuridine) and TUNEL (TdT-mediated dUTP nick-end labeling) staining assays revealed that overexpression of long noncoding RNA Gm9866 promoted cell proliferation and inhibited apoptosis. These findings thus indicated that long noncoding RNA Gm9866 promoted macrophage polarization and inhibited the nuclear factor-κB signaling pathway. Thus, long noncoding RNA Gm9866 may serve as a potential diagnostic and therapeutic target for polarization-related diseases such as infectious diseases, inflammatory diseases, liver fibrosis, and tumors.

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Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Liao

Ruan

Chen

et al. 2023

Mediators of Inflammation

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“…We speculated that, on the one hand, high expression of IL-4, IL-13, IL-6 and IL-8 promoted macrophage polarization to an M2 type, while on the other hand, high expression of IL-6 increased the binding of IL-4 and IL-13 to IL-4R, which further promoted the polarization of M2 macrophages. However, IFN-γ and GM-CSF increased in 3D- and 3D/LPS-group-derived secretome, and they could activate M1 macrophages [ 51 , 52 ]. IL-17A had contradictory effects on macrophage polarization.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Effects of Three-Dimensional Cultured Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cell-Derived Secretome on Macrophages

Shen

et al. 2023

IJMS

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Phenotypic transformation of macrophages plays important immune response roles in the occurrence, development and regression of periodontitis. Under inflammation or other environmental stimulation, mesenchymal stem cells (MSCs) exert immunomodulatory effects through their secretome. It has been found that secretome derived from lipopolysaccharide (LPS)-pretreated or three-dimensional (3D)-cultured MSCs significantly reduced inflammatory responses in inflammatory diseases, including periodontitis, by inducing M2 macrophage polarization. In this study, periodontal ligament stem cells (PDLSCs) pretreated with LPS were 3D cultured in hydrogel (termed SupraGel) for a certain period of time and the secretome was collected to explore its regulatory effects on macrophages. Expression changes of immune cytokines in the secretome were also examined to speculate on the regulatory mechanisms in macrophages. The results indicated that PDLSCs showed good viability in SupraGel and could be separated from the gel by adding PBS and centrifuging. The secretome derived from LPS-pretreated and/or 3D-cultured PDLSCs all inhibited the polarization of M1 macrophages, while the secretome derived from LPS-pretreated PDLSCs (regardless of 3D culture) had the ability to promote the polarization of M1 to M2 macrophages and the migration of macrophages. Cytokines involved in the production, migration and polarization of macrophages, as well as multiple growth factors, increased in the PDLSC-derived secretome after LPS pretreatment and/or 3D culture, which suggested that the secretome had the potential to regulate macrophages and promote tissue regeneration, and that it could be used in the treatment of inflammation-related diseases such as periodontitis in the future.

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“…Macrophage activation play a crucial role in inflammatory responses and is instrumental in the development of inflammation and associated diseases, including AAA [ 16 , 17 ]. The presence of activated macrophages in AAA contributes to the progression and exacerbation of aortic tissue degeneration, highlighting the importance of understanding the underlying mechanisms and potential therapeutic targets for the management of AAA [ 4 , 5 , 6 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages

Elbialy,

Kitauchi,

Yamanouchi

2023

IJMS

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Autophagy is a lysosomal degradation system that eliminates and recycles damaged intracellular organelles and proteins. Inflammatory macrophages play a critical role in the development of various age-related inflammatory illnesses such as abdominal aortic aneurysm, atherosclerosis, and rheumatoid arthritis; therefore, identifying the mechanisms that cause macrophage inflammation is crucial for a better understanding of and developing therapeutics for inflammatory diseases. Previous research has linked autophagy to macrophage inflammation; Atg16L1-deficient macrophages increase IL-1 and IL-18 production via inflammasome activation. In this study, however, we show an alternative pathway of macrophage inflammation in an autophagy-deficient environment. We found that inhibiting autophagy in THP1 macrophages progressively increased the expression of p65-mediated inflammatory genes. This effect was reversed by treatment with antioxidants or azd0156, an ataxia telangiectasia mutated (ATM) inhibitor. In addition, our results showed that M1 macrophages inhibit autophagy and induce DNA damage, whereas M2 macrophages activate autophagy and reduce DNA damage. Importantly, the chemical activation of autophagy or ATM inhibition during M1 polarization reduced the M1 phenotype and inflammation, whereas inhibiting autophagy during M2 polarization also reduced the M2 phenotype. Thus, our findings highlight the importance of the autophagy–ATM pathway in driving macrophage inflammation.

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Pathogenic Tconvs promote inflammatory macrophage polarization through GM‐CSF and exacerbate abdominal aortic aneurysm formation

Cited by 6 publications

References 60 publications

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Regulatory Effects of Three-Dimensional Cultured Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cell-Derived Secretome on Macrophages

Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages

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