scholarly journals ST36 Acupuncture Alleviates the Inflammation of Adjuvant-Induced Arthritic Rats by Targeting Monocyte/Macrophage Modulation

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Fuming Yang ◽  
Yinan Gong ◽  
Nannan Yu ◽  
Lin Yao ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Communication Networks ◽  
Immune Cell ◽  
Macrophage Polarization ◽  
Cell Communication ◽  
Bone Destruction ◽  
Systematic Research ◽  
Ankle Joints ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Inflammatory Action

Background. Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Acupuncture has been proven effective in RA treatment. This study aimed to investigate the anti-inflammatory action of acupuncture, specifically, in relation to immune cell interactions and key mediators. Methods. Rats with adjuvant-induced arthritics (AIA) were treated with manual acupuncture (MA) at Zusanli (ST36). Joint edema and paw withdrawal latency were monitored to observe the effects on inflammation. The levels of 24 cytokines, chemokines, and growth factors in ankle joints during the treatment (on days 1, 7, 15, and 21) were detected by multiplex immunoassay. A bioinformatics analysis based on a directed weighted mathematical model was used to construct cell communication network diagrams and identify the key cells through calculation. The monocyte/macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines. Results. ST36 MA alleviated paw edema and upregulated the nociceptive threshold of AIA rats. Several innate and adaptive immune cytokines were dynamically regulated by MA, and MA-treated rats showed a significant improvement in symptoms compared with AIA rats by day 21. The immune cell-cell communication networks were intensified with the development of RA but were significantly reduced after treatment with MA. MA was found to specifically regulate monocytes/macrophages in inflamed ankle joints ST36 MA also inhibited M1-phenotype macrophages accompanied by decreased levels of IL-1β. Conclusions. ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. This research highlighted a systematic research paradigm for investigating mechanisms of acupuncture action.

scholarly journals The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiaqi Wang ◽  
Shanshan Lu ◽  
Fuming Yang ◽  
Yi Guo ◽  
Zelin Chen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Scientific Basis ◽  
M2 Macrophage ◽  
Extrinsic Factors ◽  
Therapeutic Goals ◽  
Tissue Microenvironment ◽  
Inflammatory Conditions ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Inflammatory Action

AbstractAcupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

Abstract 553: Siglec-1 (CD169) on Monocytes/Macrophages: A New Receptor For Extracellular Self-RNA in Triggering Inflammatory Responses via the Sheddase TACE/ADAM17

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
Extracellular Rna ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: –]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.

scholarly journals Liposomal delivery of azithromycin enhances its immunotherapeutic efficacy and reduces toxicity in myocardial infarction

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ahmed Al-Darraji ◽  
Renée R. Donahue ◽  
Himi Tripathi ◽  
Hsuan Peng ◽  
Bryana M. Levitan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Immune Cell ◽  
Macrophage Polarization ◽  
Significant Shift ◽  
Inflammatory Genes ◽  
Cardiac Recovery ◽  
Inflammatory Monocytes ◽  
Acute Myocardial Injury ◽  
Anti Inflammatory ◽  
Target Effects

Abstract A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We observed a significant shift favoring reparatory/anti-inflammatory macrophages with L-AZM formulation. L-AZM use resulted in a remarkable decrease in cardiac inflammatory neutrophils and the infiltration of inflammatory monocytes. Immune cell modulation was associated with the downregulation of pro-inflammatory genes and the upregulation of anti-inflammatory genes. The immunomodulatory effects of L-AZM were associated with a reduction in cardiac cell death and scar size as well as enhanced angiogenesis. Overall, L-AZM use enhanced cardiac recovery and survival after MI. Importantly, L-AZM was protective from F-AZM cardiac off-target effects. We demonstrate that the liposomal formulation of AZM enhances the drug’s efficacy and safety in an animal model of acute myocardial injury. This is the first study to establish the immunomodulatory properties of liposomal AZM formulations. Our findings strongly support clinical trials using L-AZM as a novel and clinically relevant therapeutic target to improve cardiac recovery and reduce heart failure post-MI in humans.

scholarly journals Macrophage polarization in chronic kidney disease: a balancing act between renal recovery and decline?

2019 ◽  
Vol 317 (6) ◽  
pp. F1409-F1413 ◽  
Author(s):  
Jason E. Engel ◽  
Alejandro R. Chade
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Injury ◽  
Dynamic Balance ◽  
Macrophage Polarization ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
And Function ◽  
Injury Potential

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments, where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a proinflammatory M1 phenotype. Later in the course of healing, abundant apoptotic debris and anti-inflammatory cytokines induce the production of anti-inflammatory M2 macrophages, which contribute to tissue regeneration and repair. Thus, the dynamic balance of M1 and M2 populations may outline the burden of inflammation and process of tissue repair that define renal outcomes, which has been the impetus for therapeutic efforts targeting macrophages. This review will discuss the role of these phenotypes in the progression of chronic renal injury, potential pathogenic mechanisms, and the promise of macrophage-based therapeutic applications for chronic kidney disease.

scholarly journals Macrophage polarization is linked to Ca2+-independent phospholipase A2β-derived lipids and cross-cell signaling in mice

2019 ◽  
Vol 61 (2) ◽  
pp. 143-158 ◽  
Author(s):  
Alexander J. Nelson ◽  
Daniel J. Stephenson ◽  
Christopher L. Cardona ◽  
Xiaoyong Lei ◽  
Abdulaziz Almutairi ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Lipid Mediator ◽  
Inflammatory Phenotype ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
First Time ◽  
Genotypic Control ◽  
Hydrolysis Of ◽  
Phospholipases A

Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β−/−) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA2β.Tg mice with selective iPLA2β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA2β−/−, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA2β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF1α, PGE2, leukotriene B4) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA2 or cytosolic PLA2α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA2β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA2β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.

scholarly journals Csf1r-GCaMP5 Reporter Mice Reveal Immune Cell Communication in Vitro and in Vivo

2021 ◽  
Author(s):  
N Taghdiri ◽  
D Calcagno ◽  
Z Fu ◽  
K Huang ◽  
RH Kohler ◽  
...  
Keyword(s):  
Communication Networks ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Communication ◽  
Spatiotemporal Dynamics ◽  
The Body ◽  
Excitable Cells ◽  
Communication Events

ABSTRACTInterconnected cells are responsible for emergent functions ranging from cognition in the brain to cyclic contraction in the heart. In electrically excitable cells, methods for studying cell communication are highly advanced, but in non-excitable cells, generalized methods for studying cell communication are less mature. Immune cells have generally been classified as non-excitable cells with diverse pathophysiologic roles that span every tissue in the body, yet little is known about their interconnectedness because assays are destructive and have low temporal resolution. In this work, we hypothesize that non-excitable immune cells are functionally interconnected in previously unrecognized cell communication networks. To test the hypothesis, we created a hematopoietic calcium reporter mouse (Csf1r-Cre × GCaMP5) and non-destructively quantified the spatiotemporal dynamics of intracellular calcium in vitro and in vivo. In vitro, bone marrow derived macrophages calcium reporters reveal that fatal immune stimulatory DNA-sensing induces rapid intercellular communication to neighboring cells. In vivo, using intravital microscopy through a dorsal window chamber in the context of MC38-H2B-mCherry tumors, Csf1r-GCaMP5 reporters exhibit spatiotemporal dynamics consistent with cell communication. We present a theoretical framework and analysis pipeline for identifying spatiotemporal locations of “excess synchrony” of calcium spiking as a means of inferring previously unrecognized cell communication events. Together, these methods provide a toolkit for investigating known and as-yet-undiscovered cell communication events in vitro and in vivo.

scholarly journals Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Laura Dugo ◽  
Maria Giovanna Belluomo ◽  
Chiara Fanali ◽  
Marina Russo ◽  
Francesco Cacciola ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Total Phenolic ◽  
Macrophage Response ◽  
Beneficial Effects ◽  
Polyphenolic Extract ◽  
M1 Macrophage ◽  
Inflammatory State ◽  
M1 Phenotype ◽  
Anti Inflammatory

Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γfor M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

scholarly journals Pinosylvin Shifts Macrophage Polarization to Support Resolution of Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2772
Author(s):  
Konsta Kivimäki ◽  
Tiina Leppänen ◽  
Mari Hämäläinen ◽  
Katriina Vuolteenaho ◽  
Eeva Moilanen
Keyword(s):  
Macrophage Activation ◽  
Environmental Changes ◽  
Macrophage Polarization ◽  
Resolution Of Inflammation ◽  
Human Macrophages ◽  
Arginase 1 ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
M1 Type ◽  
M2 Phenotype

Pinosylvin is a natural stilbenoid found particularly in Scots pine. Stilbenoids are a group of phenolic compounds identified as protective agents against pathogens for many plants. Stilbenoids also possess health-promoting properties in humans; for instance, they are anti-inflammatory through their suppressing action on proinflammatory M1-type macrophage activation. Macrophages respond to environmental changes by polarizing towards proinflammatory M1 phenotype in infection and inflammatory diseases, or towards anti-inflammatory M2 phenotype, mediating resolution of inflammation and repair. In the present study, we investigated the effects of pinosylvin on M2-type macrophage activation, aiming to test the hypothesis that pinosylvin could polarize macrophages from M1 to M2 phenotype to support resolution of inflammation. We used lipopolysaccharide (LPS) to induce M1 phenotype and interleukin-4 (IL-4) to induce M2 phenotype in J774 murine and U937 human macrophages, and we measured expression of M1 and M2-markers. Interestingly, along with inhibiting the expression of M1-type markers, pinosylvin had an enhancing effect on the M2-type activation, shown as an increased expression of arginase-1 (Arg-1) and mannose receptor C type 1 (MRC1) in murine macrophages, and C-C motif chemokine ligands 17 and 26 (CCL17 and CCL26) in human macrophages. In IL-4-treated macrophages, pinosylvin enhanced PPAR-γ expression but had no effect on STAT6 phosphorylation. The results show, for the first time, that pinosylvin shifts macrophage polarization from the pro-inflammatory M1 phenotype towards M2 phenotype, supporting resolution of inflammation and repair.

scholarly journals Boi-ogi-to (TJ-20), a Kampo Formula, Suppresses the Inflammatory Bone Destruction and the Expression of Cytokines in the Synovia of Ankle Joints of Adjuvant Arthritic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xinwen Zhang ◽  
Zhou Wu ◽  
Yicong Liu ◽  
Junjun Ni ◽  
Chunfu Deng ◽  
...  
Keyword(s):  
Scientific Evidence ◽  
Bone Destruction ◽  
Scientific Basis ◽  
Helper T Cells ◽  
Therapeutic Effects ◽  
Main Function ◽  
Dependent Manner ◽  
Ankle Joints ◽  
Anti Inflammatory ◽  
Inflammatory Effect

TJ-20 is a formula consisting of 6 herbs that has been used in the clinical treatment of rheumatoid arthritis (RA) in China and Japan for centuries. However, scientific evidence of the effects of TJ-20 has not been established. In the present study, we focused on the therapeutic effects and investigated the main function of TJ-20 on adjuvant arthritis (AA), an animal model of RA, which was induced with complete Freund’s adjuvant (CFA). TJ-20 was administered orally at 600 mg/kg once a day from 0, 7, and 10 days to 8 weeks after the CFA treatment. TJ-20 significantly ameliorated inflammatory progression and bone destruction in AA in a time-dependent manner. Furthermore, TJ-20 significantly reduced the increased changes in a number of macrophages and helper T cells. Moreover, TJ-20 suppressed the expression of TNF-αwhereas it augmented the expression of IL-10 and attenuated Th1 cells responses in the synovia of the ankle joint. Therefore, TJ-20 regulated the expression of proinflammatory and anti-inflammatory cytokines in macrophages and Th1/Th2 balance in the synovia of ankle joints in AA rats. These results suggest the positive anti-inflammatory effect of TJ-20 and provide a scientific basis for the clinical use of TJ-20 for RA.

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