Neutrophil recruitment mediated by sphingosine 1-phosphate (S1P)/S1P receptors during chronic liver injury

Zhao, Xinhao; Yang, Le; Chang, Na; Hou, Lei; Zhou, Xuan; Dong, Chengbin; Liu, Fuquan; Yang, Lin; Li, Liying

doi:10.1016/j.cellimm.2020.104243

Cited by 21 publications

(23 citation statements)

References 51 publications

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“…S1P is emerging as an important mediator in immune and inflammatory disorders [56], and the expression of the G-protein coupled S1PR has been studied for various immune cells like mast cells, eosinophils, and neutrophils. The effects of stimulating S1PR-expressing cells with S1P range from chemotaxis in eosinophils and neutrophils [52,53,57] to amplification of degranulation and cytokine release in mast cells [47,58] and the redirection of neutrophil apoptosis to the formation of neutrophil extracellular traps (NETs) during liver injury [59]. As basophils are the only type of granulocyte in which S1PR expression has yet to be studied, we were curious to see if we could produce similar findings to eosinophils and neutrophils in receptor expression and function for basophils.…”

Section: Discussionmentioning

confidence: 99%

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients

Gray

Limberg

Wiebe

et al. 2022

IJMS

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Basophils are key effector cells in atopic diseases, and the signaling sphingolipid Sphigosine-1-phosphate (S1P) is emerging as an important mediator in these conditions. The possible interaction of S1P and basophils and the resulting biological effects have not yet been studied. We hypothesize that S1P influences the function of basophils in atopy and aim to elucidate the modes of interaction. S1P receptor (S1PR) expression in human peripheral blood basophils from atopic and non-atopic patients was assessed through qRT-PCR and flow cytometry analysis. Functional effects of S1P were assessed through a basophil activation test (BAT), calcium flux, apoptosis, and chemotaxis assays. Immunofluorescence staining was performed to visualize intracellular S1P. Human basophils express S1PR1, S1PR2, S1PR3, and S1PR4 on the mRNA level. 0.1 µM S1P have anti-apoptotic, while 10 µM exhibits apoptotic effects on basophils. Basophils from atopic patients show less chemotactic activity in response to S1P than those from healthy donors. Protein expression of S1PR1 is downregulated in atopic patients, and basophils in lesional AD skin possess intracellular S1P. These findings suggest that the interaction of S1P and basophils might be an important factor in the pathophysiology of atopy.

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Section: Discussionmentioning

confidence: 99%

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients

Gray

Limberg

Wiebe

et al. 2022

IJMS

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“…Bone marrow-derived neutrophils were obtained from 6-week-old ICR mice as described ( 23 ). Bone marrow cells were extracted from the tibias and femur by flushing with PBS using a 25G needle, filter with 70 µm cell strainer.…”

Section: Methodsmentioning

confidence: 99%

Activated Neutrophils Secrete Chitinase-Like 1 and Attenuate Liver Inflammation by Inhibiting Pro-Inflammatory Macrophage Responses

Chang

Zhao

et al. 2022

Front. Immunol.

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Excessive activation and recruitment of neutrophils are generally considered to be associated with pathological aggravation of multiple diseases. However, as the role of neutrophils in tissue injury repair is receiving increasing attention, it is necessary to further explore the beneficial role of activated neutrophils in promoting the resolution of inflammation after injury. In this study, we found that activated neutrophils have a crucial function in suppressing liver inflammation. In methionine-choline-deficient and high-fat (MCDHF) diet induced liver inflammation in mice, tail vein injection of activated neutrophils (A-Neu, stimulated by sphingosine 1-phosphate) inhibited the expressions of pro-inflammatory cytokines in the liver, including C-C chemokine motif ligand 4, tumor necrosis factor and nitric oxide synthase 2, and attenuated liver injury. However, non-activated neutrophils (N-Neu) did not have these effects. In vitro, pro-inflammatory macrophages were co-cultured with N-Neu or A-Neu by transwell, respectively. A-Neu was found to suppress the pro-inflammatory phenotype of macrophages by using RT-qPCR, western blot and cytometric bead array. Microarray analysis showed that there were systematic variations in transcript expression levels between N-Neu and A-Neu. GeneVenn software was used to show the gene expression overlap between GO terms including Regulation of Cell Communication, Cytokine Secretion, Inflammatory Response and Extracellular Space clusters. We identified that Chitinase-like 1 (CHIL1) secreted by S1P activated neutrophils may be an important mediators affecting the pro-inflammatory macrophage responses. In the injured liver of mice induced by MCDHF diet, the expression of Chil1 mRNA increased and was positively correlated with the neutrophil marker Ly6g. Moreover, the secretion of CHIL1 in A-Neu increased significantly. Strikingly, the effect of A-Neu on macrophage response was reproduced by incubating pro-inflammatory macrophages with recombinant CHIL1. A-Neu conditioned medium were incubated with CHIL1 antibody-conjugated protein G beads, magnetically separated to immunodepletion CHIL1 from the A-Neu supernatant, which can partially weaken its inhibitory effect of A-Neu on the production of macrophage pro-inflammatory cytokines. Together, the conclusions indicated that A-Neu could inhibit the pro-inflammatory macrophage responses by secreting CHIL1, thereby effectively inhibiting liver inflammation.

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“…There have also been extensive studies into the effects of S1PR2 signaling in neutrophils. Zhao X. et al studied the roles of S1PR2 activation in neutrophils utilizing a neutrophil migration assay and found that inhibition of S1PR2 with JTE-013 in murine bone marrow neutrophils led to significantly less migration (44). S1PR2 antagonism also decreased neutrophil F-actin, suggesting that S1PR2 is important in neutrophil cytoskeletal remodeling.…”

Section: S1pr2mentioning

confidence: 99%

Bile acids as inflammatory mediators and modulators of intestinal permeability

et al. 2022

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Bile acids are critical for the digestion and absorption of lipids and fat-soluble vitamins; however, evidence continues to emerge supporting additional roles for bile acids as signaling molecules. After they are synthesized from cholesterol in the liver, primary bile acids are modified into secondary bile acids by gut flora contributing to a diverse pool and making the composition of bile acids highly sensitive to alterations in gut microbiota. Disturbances in bile acid homeostasis have been observed in patients with Inflammatory Bowel Diseases (IBD). In fact, a decrease in secondary bile acids was shown to occur because of IBD-associated dysbiosis. Further, the increase in luminal bile acids due to malabsorption in Crohn’s ileitis and ileal resection has been implicated in the induction of diarrhea and the exacerbation of inflammation. A causal link between bile acid signaling and intestinal inflammation has been recently suggested. With respect to potential mechanisms related to bile acids and IBD, several studies have provided strong evidence for direct effects of bile acids on intestinal permeability in porcine and rodent models as well as in humans. Interestingly, different bile acids were shown to exert distinct effects on the inflammatory response and intestinal permeability that require careful consideration. Such findings revealed a potential effect for changes in the relative abundance of different bile acids on the induction of inflammation by bile acids and the development of IBD. This review summarizes current knowledge about the roles for bile acids as inflammatory mediators and modulators of intestinal permeability mainly in the context of inflammatory bowel diseases.

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Neutrophil recruitment mediated by sphingosine 1-phosphate (S1P)/S1P receptors during chronic liver injury

Cited by 21 publications

References 51 publications

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients

Activated Neutrophils Secrete Chitinase-Like 1 and Attenuate Liver Inflammation by Inhibiting Pro-Inflammatory Macrophage Responses

Bile acids as inflammatory mediators and modulators of intestinal permeability

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