scholarly journals Enteric glial cells favour accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation

2021 ◽  
Author(s):  
Michelle Stakenborg ◽  
Saeed Abdurahiman ◽  
Veronica De Simone ◽  
Gera Goverse ◽  
Nathalie Stakenborg ◽  
...  
Keyword(s):  
Glial Cells ◽  
Intestinal Inflammation ◽  
Mononuclear Phagocyte ◽  
Inflammatory Factors ◽  
Monocyte Differentiation ◽  
Enteric Glial Cells ◽  
Monocyte Recruitment ◽  
Microenvironmental Factors ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Objective: Monocyte-derived macrophages (Mϕs) are crucial regulators during muscularis inflammation. However, it is unclear which microenvironmental factors are responsible for monocyte recruitment and neurotrophic Mϕ differentiation in this paradigm. Here, we investigate Mϕ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue protective Mϕs. Design: Single cell RNA sequencing was performed on immune cells from the muscularis of wild-type and CCR2-/- mice at different timepoints after muscularis inflammation. CX3CR1GFP/+ and CX3CR1CreERT2 R26YFP mice were analyzed by flow cytometry and immunofluorescence. The transcriptome of enteric glial cells (EGCs) was investigated using PLPCreERT2 Rpl22HA mice. In addition, we assessed the effect of supernatant from neurosphere-derived EGCs on monocyte differentiation based on the expression of pro- and anti-inflammatory factors. Results: Muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c+ monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mϕs subpopulations during the resolution of muscularis inflammation, i.e. Cd206+ MhcIIhi and Timp2+ MhcIIlo Mϕs, which were both derived from CCR2+ monocytes. Interestingly, we found that EGCs were able to sense damage to the muscularis to stimulate monocyte recruitment and differentiation towards pro-resolving Mϕs via CCL2 and CSF1, respectively. Conclusion: Our study provides a comprehensive insight into pro-resolving Mϕ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mϕs, thereby highlighting pro-resolving Mϕ differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.

scholarly journals Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

2020 ◽  
Author(s):  
Fuyu Duan ◽  
Liyan Guo ◽  
Liuliu Yang ◽  
Yuling Han ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Early Stage ◽  
Synergistic Effects ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Lung Cells ◽  
Alveolar Type ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Abstract Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.

scholarly journals The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Boxun Zhang ◽  
Rensong Yue ◽  
Yuan Chen ◽  
Xiaoying Huang ◽  
Maoyi Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Diabetic Rats ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
Pathological State ◽  
Intestinal Mucosal Barrier ◽  
Metabolic Inflammation ◽  
Anti Inflammatory

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

scholarly journals Neutrophil Extracellular Traps Reprogram IL-4/GM-CSF-Induced Monocyte Differentiation to Anti-inflammatory Macrophages

2017 ◽  
Vol 8 ◽  
Author(s):  
Anderson B. Guimarães-Costa ◽  
Natalia C. Rochael ◽  
Fabiano Oliveira ◽  
Juliana Echevarria-Lima ◽  
Elvira M. Saraiva
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Monocyte Differentiation ◽  
Gm Csf ◽  
Extracellular Traps ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

scholarly journals Limited Impact of 6-Mercaptopurine on Inflammation-Induced Chemokines Expression Profile in Primary Cultures of Enteric Nervous System

2021 ◽  
Author(s):  
Jan Kneusels ◽  
Meike Kaehler ◽  
Ingolf Cascorbi ◽  
Thilo Wedel ◽  
Michel Neunlist ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Intestinal Inflammation ◽  
Primary Cultures ◽  
Cellular Mechanisms ◽  
Inflammatory Stress ◽  
Cytokines And Chemokines ◽  
Enteric Glial Cells ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory

AbstractIncreasing evidences indicate that the enteric nervous system (ENS) and enteric glial cells (EGC) play important regulatory roles in intestinal inflammation. Mercaptopurine (6-MP) is a cytostatic compound clinically used for the treatment of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease. However, potential impacts of 6-MP on ENS response to inflammation have not been evaluated yet. In this study, we aimed to gain deeper insights into the profile of inflammatory mediators expressed by the ENS and on the potential anti-inflammatory impact of 6-MP in this context. Genome-wide expression analyses were performed on ENS primary cultures exposed to lipopolysaccharide (LPS) and 6-MP alone or in combination. Differential expression of main hits was validated by quantitative real-time PCR (qPCR) using a cell line for EGC. ENS cells expressed a broad spectrum of cytokines and chemokines of the C-X-C motif ligand (CXCL) family under inflammatory stress. Induction of Cxcl5 and Cxcl10 by inflammatory stimuli was confirmed in EGC. Inflammation-induced protein secretion of TNF-α and Cxcl5 was partly inhibited by 6-MP in ENS primary cultures but not in EGC. Further work is required to identify the cellular mechanisms involved in this regulation. These findings extend our knowledge of the anti-inflammatory properties of 6-MP related to the ENS and in particular of the EGC-response to inflammatory stimuli.

Macrophages in Kidney Injury, Inflammation, and Fibrosis

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Qi Cao ◽  
David C. H. Harris ◽  
Yiping Wang
Keyword(s):  
Kidney Disease ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Treatment Options ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Anti Inflammatory ◽  
Molecular Patterns ◽  
Inflammatory Macrophages

Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. Macrophages are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics in response to various stimuli in the local microenvironment in different types of kidney disease. In kidney tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce pro-inflammatory macrophages, which contribute to further tissue injury, inflammation, and subsequent fibrosis. Apoptotic cells and anti-inflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. This review summarizes the role of macrophages with different phenotypes in kidney injury, inflammation, and fibrosis in various acute and chronic kidney diseases. Understanding alterations of kidney microenvironment and the factors that control the phenotype and functions of macrophages may offer an avenue for the development of new cellular and cytokine/growth factor-based therapies as alternative treatment options for patients with kidney disease.

scholarly journals Atypical Activin A and IL-10 Production Impairs Human CD16+Monocyte Differentiation into Anti-Inflammatory Macrophages

2016 ◽  
Vol 196 (3) ◽  
pp. 1327-1337 ◽  
Author(s):  
Érika González-Domínguez ◽  
Ángeles Domínguez-Soto ◽  
Concha Nieto ◽  
José Luis Flores-Sevilla ◽  
Mariana Pacheco-Blanco ◽  
...  
Keyword(s):  
Activin A ◽  
Monocyte Differentiation ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

scholarly journals Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Xia ◽  
Yitong Liu ◽  
Guiyang Xia ◽  
Yi Liu ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Critical Role ◽  
Isoquinoline Alkaloid ◽  
Inflammatory Factors ◽  
Skin Wound Healing ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

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