scholarly journals Systemic overexpression of C-C motif chemokine ligand 2 promotes metabolic dysregulation and premature death in mice with accelerated aging

Aging ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 20001-20023
Author(s):  
Fedra Luciano-Mateo ◽  
Noemí Cabré ◽  
Gerard Baiges-Gaya ◽  
Salvador Fernández-Arroyo ◽  
Anna Hernández-Aguilera ◽  
...  
Keyword(s):  
Accelerated Aging ◽  
Premature Death ◽  
Metabolic Dysregulation ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2

scholarly journals Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Esther Rodríguez-Gallego ◽  
Marta Riera-Borrull ◽  
Anna Hernández-Aguilera ◽  
Roger Mariné-Casadó ◽  
Anna Rull ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Chemokine Receptors ◽  
Embryonic Stem ◽  
Premature Death ◽  
High Energy ◽  
Noncommunicable Diseases ◽  
Low Grade ◽  
Metabolic Disturbances ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2

Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.

scholarly journals Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2

2006 ◽  
Vol 177 (11) ◽  
pp. 8072-8079 ◽  
Author(s):  
Julia L. Gregory ◽  
Eric F. Morand ◽  
Sonja J. McKeown ◽  
Jennifer A. Ralph ◽  
Pamela Hall ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Cc Chemokine ◽  
Macrophage Recruitment ◽  
Chemokine Ligand ◽  
Cc Chemokine Ligand 2 ◽  
Chemokine Ligand 2

scholarly journals MiR-144-3p is associated with pathological inflammation in patients infected with Mycobacteroides abscessus

2021 ◽  
Vol 53 (1) ◽  
pp. 136-149
Author(s):  
Hyeon Ji Kim ◽  
In Soo Kim ◽  
Sung-Gwon Lee ◽  
Young Jae Kim ◽  
Prashanta Silwal ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Nontuberculous Mycobacteria ◽  
Expression Profiles ◽  
Host Factors ◽  
Integrated Analysis ◽  
Peripheral Blood Mononuclear ◽  
Global Health Issue ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2

AbstractInfection with rapidly growing nontuberculous mycobacteria is emerging as a global health issue; however, key host factors remain elusive. Here, we investigated the characteristic immune profiles of peripheral blood mononuclear cells (PBMCs) from patients infected with Mycobacteroides abscessus subsp. abscessus (Mabc) and M. abscessus subsp. massiliense (Mmass). Using an integrated analysis of global mRNA and microRNA expression profiles, we found that several inflammatory cytokines/chemokines [interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand 2, and C-C motif chemokine ligand 2] and miR-144-3p were significantly upregulated in PBMCs from patients compared with those from healthy controls (HCs). Notably, there was a strong correlation between the expression levels of miR-144-3p and proinflammatory cytokines/chemokines. Similarly, upregulated expression of miR-144-3p and proinflammatory cytokines/chemokines was found in macrophages and lungs from mice after infection with Mabc and Mmass. We showed that the expression of negative regulators of inflammation (SARM1 and TNIP3) was significantly downregulated in PBMCs from the patients, although they were not putative targets of miR-144-3p. Furthermore, overexpression of miR-144-3p led to a marked increase in proinflammatory cytokines/chemokines and promoted bacterial growth in macrophages. Together, our results highlight the importance of miR-144-3p linking to pathological inflammation during M. abscessus infection.

scholarly journals NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Bing Li ◽  
Zhi-Peng Qi ◽  
Dong-Li He ◽  
Zhang-Han Chen ◽  
Jing-Yi Liu ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Acceptor Site ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Chemokine Ligand ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Chemokine Ligand 2

Abstract Background NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. Methods NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. Results NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. Conclusions We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

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