Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury

Zhuang, Quan; Ou, Jiarui; Zhang, Sheng; Ming, Yingzi

doi:10.2174/1389203720666190305165722

Cited by 39 publications

(38 citation statements)

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“…CX3CL1 is an adipocyte-derived inflammatory chemokine which is also up-regulated in obesity and during inflammatory processes in the CNS [ 119 ]. CX3CL1 is widely expressed in neurons located in forebrain structures involved in addiction, such as the amygdala, the prefrontal cortex and the striatum [ 120 ].…”

Section: Discussionmentioning

confidence: 99%

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

González-Portilla

Montagud‐Romero

Navarrete

et al. 2021

IJMS

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Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.

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Section: Discussionmentioning

confidence: 99%

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

González-Portilla

Montagud‐Romero

Navarrete

et al. 2021

IJMS

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“…The membrane-bound form is associated with cell adhesion. The CX3CRL1-CX3CR1 interaction often has a proinflammatory effect through the JAK-STAT, Toll-like receptor, MAPK, AKT, NF-κB, or other pathways, but can also have an anti-inflammatory effect depending on the tissue, cell type, and local environment [ 91 , 92 , 93 ]. The CX3CL1-CX3CR1 interaction has been linked to a number of diseases, including cardiac, lung, neoplastic, neurologic, and rheumatologic disease [ 90 , 91 , 94 , 95 ].…”

Section: Binding To and Infection Of Cellsmentioning

confidence: 99%

Functional Features of the Respiratory Syncytial Virus G Protein

Anderson

Jadhao

Paden

et al. 2021

Viruses

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Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.

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“…Moreover, the limited human data is strengthened by the multiple data types linking mouse and human data. For instance, endothelial CXCL9 and 10 binds to CXCR3 on lymphocytes, NK and dendritic cells executing activation, migration and differentiation of T cells [ 27 ]; chemokine C-X3-C motif ligand 1 (CX3CL1), a stimulator of vascular smooth muscle cells from endothelium binds to CX3CR1 on lymphocytes executing chemotactic and leukocyte traffic [ 59 ]; macrophage inflammatory protein 1 (MIP1a) and Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) produced by macrophages and lymphocytes bind to CCR4 on T cells maintaining chemotactic and immune cell homeostasis and obviously, elevated expression of CXCR3 [ 60 ] or CX3CR1 [ 61 ] or CCR4 [ 62 ] are implicated in PAH. A comparative analysis of CyTOF findings between KCNK3 and BMPR2 HPAH patients (data not shown for this ongoing study) suggest that these markers are uniquely associated with KCNK3 mutation, which clearly reinforces our observation and the ensuing conclusion.…”

Section: Discussionmentioning

confidence: 99%

KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models

West

Austin

Rizzi

et al. 2021

IJMS

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Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.

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Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury

Cited by 39 publications

References 1 publication

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

Functional Features of the Respiratory Syncytial Virus G Protein

KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models

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