Brief Report: Autocrine Cytokine–Mediated Deficiency of TRAIL‐Induced Monocyte Apoptosis in Rheumatoid Arthritis

Meusch, Undine; Klingner, Maria; Mathar, Christoph; Malysheva, O.; Baerwald, Christoph; Rossol, Manuela; Wagner, Ulf

doi:10.1002/art.39138

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…After dust entered the alveoli, AMs were activated by phagocytosis of dust particles, and caspase‐dependent apoptosis occurred (Bai et al, ). Apoptosis may be initiated through the cell surface receptor of AM with its ligand combination, which is mainly achieved through the induction of apoptosis in three basic signal transduction pathways: Fas–Fas‐L pathway, TNF‐α–TNFR pathway, and TRAILR–TRAIL pathway (Lin et al, ; Meusch et al, ; Zhang et al, ). AMs are key regulatory cells in lung; however, the role of apoptotic AM in lung inflammatory and fibrotic lung disorders remains to be well characterized (L. Wang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Retracted: TNF‐α–TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis

Qin

Cao

Wang

et al. 2018

Journal Cellular Physiology

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Objective: Exposure to coal dust causes the development of coal worker's pneumoconiosis (CWP), which is associated with accumulating macrophages in the lower respiratory tract. This study was performed to investigate the effect of tumor necrosis factor-α (TNF-α)-tumor necrosis factor receptor (TNFR) signal pathway on autophagy and apoptosis of alveolar macrophages (AMs) in CWP.Methods: AMs from controls exposed to coal dust and CWP patients were collected, in which expressions of TNF-α and TNFR1 were determined. Autophagy was observed by transmission electron microscopy, and apoptosis by light microscope and using terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. AMs in CWP patients were treated with TNF-α or anti-TNF-α antibody. Besides, expressions of autophagy marker proteins, apoptosis-related factors, FAS, caspase-8, and receptor-interacting serine-threonine-protein kinase 3 (RIPK3) were determined by western Blot. Activities of caspase-3 and caspase-8 were determined by a fluorescence kit. Flow cytometry was applied to measure the expression of TNFR1 on the surface of the AM. Results: TNF-α expression and TNFR1 expression on the surface of AM, as well as autophagy and apoptotic index were significantly increased in AMs of CWP patients. In response to the treatment of TNF-α, TNF-α expression and TNFR1 expression on the surface of AM as well as LC3I expression were increased, autophagy was decreased, and LC3, LC3II, Beclin1 and B-cell lymphoma 2 expressions decreased, whereas FAS expression and activity and expression of caspase-3 and caspase-8 increased, and apoptotic index increased. Moreover, the situations were reversed with the treatment of anti-TNF-α antibody. Conclusion: TNF-α-TNFR signal pathway was involved in the occurrence and development of CWP by activating FAS-caspase-8 and thus inhibiting autophagy while promoting apoptosis of AM. K E Y W O R D S alveolar macrophage, apoptosis, autophagy, signal pathway, TNF-α-TNFR

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Section: Discussionmentioning

confidence: 99%

Retracted: TNF‐α–TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis

Qin

Cao

Wang

et al. 2018

Journal Cellular Physiology

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“…The CpG islands in the promoter region of the DR3 gene were hypermethylated, where inverse correlation existed in the levels of serum DR3 protein and promoter CpG methylation in rheumatoid synovia ( 60 ). In relationship to DR3, TRAIL-induced apoptosis has been shown to be defective in the monocytes of RA patients ( 60 ), and the decoy receptor 3 that protects cells from Fas-induced apoptosis was also over-represented in RA ( 61 , 62 ).…”

Section: Discussionmentioning

confidence: 99%

A variant of death-receptor 3 associated with rheumatoid arthritis interferes with apoptosis-induction of T cell

Hashiramoto

Konishi

Murayama

et al. 2018

Journal of Biological Chemistry

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Rheumatoid arthritis (RA) is a chronic polyarthritis of unknown etiology. To unravel the molecular mechanisms in RA, we performed targeted DNA sequencing analysis of patients with RA. This analysis identified a variant of the death receptor 3 (DR3) gene, a member of the family of apoptosis-inducing Fas genes, which contains four single-nucleotide polymorphisms (SNPs) and a 14-nucleotide deletion within exon 5 and intron 5. We found that the deletion causes the binding of splicing regulatory proteins to DR3 pre-mRNA intron 5, resulting in a portion of intron 5 becoming part of the coding sequence, thereby generating a premature stop codon. We also found that this truncated DR3 protein product lacks the death domain and forms a heterotrimer complex with wildtype DR3 that dominant-negatively inhibits ligand-induced apoptosis in lymphocytes. Myelocytes from transgenic mice expressing the human DR3 variant produced soluble truncated DR3, forming a complex with TNF-like ligand 1A (TL1A), which inhibited apoptosis induction. In summary, our results reveal that a DR3 splice variant that interferes with ligand-induced T cell responses and apoptosis may contribute to RA pathogenesis.

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“…In the first study case, on the one hand, we found that the differentially expressed genes (such as CREB1 [ 42 , 43 ], TNFSF10 [ 44 ], CD4 [ 45 ], and TNFSF12 [ 46 ]), and the non-differentially expressed genes (such as ESR1 [ 47 ], VDR [ 48 ], PPARG [ 49 ], ESR2 [ 50 ]) are RA-related genes. On the other hand, we also found that some of the hub nodes in the network are not included in the RA-related gene dataset, such as differentially expressed genes GSK3B , SMARCA4 , PSMD7 , TGFBR1 , and so forth, and non-differentially expressed genes HNF4A , PGR , RXRA , ESRRA , and so forth.…”

Section: Discussionmentioning

confidence: 99%

Knowledge-Based Neuroendocrine Immunomodulation (NIM) Molecular Network Construction and Its Application

Wang¹,

Han²,

Zhang³

et al. 2018

Molecules

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Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer’s disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM).

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Brief Report: Autocrine Cytokine–Mediated Deficiency of TRAIL‐Induced Monocyte Apoptosis in Rheumatoid Arthritis

Cited by 7 publications

References 15 publications

Retracted: TNF‐α–TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis

Retracted: TNF‐α–TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis

A variant of death-receptor 3 associated with rheumatoid arthritis interferes with apoptosis-induction of T cell

Knowledge-Based Neuroendocrine Immunomodulation (NIM) Molecular Network Construction and Its Application

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