Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature

2016 ◽  
Vol 397 (10) ◽  
pp. 981-993 ◽  
Author(s):  
Thomas Gobbetti ◽  
Sadani N. Cooray
Keyword(s):  
Tissue Repair ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Molecular Targets ◽  
Biological Properties ◽  
Innate Immune ◽  
Therapeutic Effects ◽  
Annexin A1 ◽  
Persistent Inflammation ◽  
Tissue Healing

AbstractInflammation is essential to protect the host from exogenous and endogenous dangers that ultimately lead to tissue injury. The consequent tissue repair is intimately associated with the fate of the inflammatory response. Restoration of tissue homeostasis is achieved through a balance between pro-inflammatory and anti-inflammatory/pro-resolving mediators. In chronic inflammatory diseases such balance is compromised, resulting in persistent inflammation and impaired healing. During the last two decades the glucocorticoid-regulated protein Annexin A1 (AnxA1) has emerged as a potent pro-resolving mediator acting on several facets of the innate immune system. Here, we review the therapeutic effects of AnxA1 on tissue healing and repairing together with the molecular targets responsible for these complex biological properties.

scholarly journals Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Yizhuo Wang ◽  
Meng Zhao ◽  
Shuyun Liu ◽  
Jun Guo ◽  
Yanrong Lu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Biological Function ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Bioactive Molecules ◽  
Live Cells ◽  
Therapeutic Effects ◽  
Innate Immune Cells ◽  
Beneficial Effects

Abstract Macrophages (Mφ) are primary innate immune cells that exhibit diverse functions in response to different pathogens or stimuli, and they are extensively involved in the pathology of various diseases. Extracellular vesicles (EVs) are small vesicles released by live cells. As vital messengers, macrophage-derived EVs (Mφ-EVs) can transfer multiple types of bioactive molecules from macrophages to recipient cells, modulating the biological function of recipient cells. In recent years, Mφ-EVs have emerged as vital mediators not only in the pathology of multiple diseases such as inflammatory diseases, fibrosis and cancers, but also as mediators of beneficial effects in immunoregulation, cancer therapy, infectious defense, and tissue repair. Although many investigations have been performed to explore the diverse functions of Mφ-EVs in disease pathology and intervention, few studies have comprehensively summarized their detailed biological roles as currently understood. In this review, we briefly introduced an overview of macrophage and EV biology, and primarily focusing on current findings and future perspectives with respect to the pathological and therapeutic effects of Mφ-EVs in various diseases.

scholarly journals Age-related Immune-Stromal Networks Inhibit Response to Regenerative Immunotherapies

2021 ◽  
Author(s):  
Jin Han ◽  
Christopher Cherry ◽  
Anna Ruta ◽  
David R. Maestas ◽  
Joscelyn C. Mejias ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Neutralizing Antibodies ◽  
Tissue Repair ◽  
Therapeutic Response ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Communication Analysis ◽  
Age Related ◽  
Immunological Changes ◽  
Immune Changes

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Indeed, regenerative medicine strategies designed to promote tissue repair are now focusing on the immune system as a therapeutic target due to its role in response to tissue damage and regulation of tissue repair. However, age-related immune changes to the response to damage and the resulting impact on repair remains unknown. Here, we characterized age-related immunological changes that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix (ECM). We found that aging reduced the response of interleukin (IL)4 producing eosinophils and CD4 T cells in a volumetric muscle injury treated with ECM leading to reduced repair and increased fibrosis. Single cell RNA sequencing and cell-cell communication analysis via transcription factor (TF) activation revealed diminished interactions between immune and stromal modules in aging animals. Validation of the age-specific TFs and predicated protein interactions in the tissue and draining lymph nodes found multiple genes activated in old animals only after injury that were primarily related to IL17 signaling. Local inhibition of age-related type 3 immune activation using IL17-neutralizing antibodies restored therapeutic response to ECM and promoted muscle repair in older animals through increased recruitment of IL4 producing immune cells and regenerating muscle fibers. Altogether, innate and adaptive immune changes that occur with aging, in combination with dysregulated stromal communication, contribute to an impaired response to tissue injury which can be overcome with combination immunotherapy.

scholarly journals Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design

2016 ◽  
Vol 241 (10) ◽  
pp. 1084-1097 ◽  
Author(s):  
Molly E Ogle ◽  
Claire E Segar ◽  
Sraeyes Sridhar ◽  
Edward A Botchwey
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Critical Role ◽  
Myeloid Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Signaling Systems ◽  
Monocytes And Macrophages

Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their implantation.

scholarly journals Drug delivery strategies to control macrophages for tissue repair and regeneration

2016 ◽  
Vol 241 (10) ◽  
pp. 1054-1063 ◽  
Author(s):  
Reham Garash ◽  
Anamika Bajpai ◽  
Brandon M Marcinkiewicz ◽  
Kara L Spiller
Keyword(s):  
Drug Delivery ◽  
Tissue Repair ◽  
Chronic Wounds ◽  
Cellular Therapy ◽  
Inflammatory Diseases ◽  
Macrophage Phenotype ◽  
Tissue Repair And Regeneration ◽  
Complex Process ◽  
Tissue Healing ◽  
Delivery Strategies

Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body’s response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies.

scholarly journals The Effect of Allicin on Innate Immune Genes of Common Carp (Cyprinus carpio L)

2015 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
Jean Fall ◽  
Mahmoud Tanekhy
Keyword(s):  
Inflammatory Diseases ◽  
Head Kidney ◽  
Innate Immune ◽  
Therapeutic Effects ◽  
Immune Genes ◽  
Glucose Levels ◽  
Tnf Α ◽  
Innate Immune Genes ◽  
The Impact ◽  
Pro Inflammatory Cytokines

<p>Garlic is known to possess a vast variety of biological functions. It was reported to be ana a antimicrobial, antithrombotic, anticacer, antioxidant and could improve the immune-system as well as had the capacity to lower serum lipid and glucose levels. The impact of allicin on signaling pathways still needs to be investigated and reports about its effect on cytokine production are inconsistent. In the present study, we investigated the influence of allicin on several carp genes and checked the immediate response of these genes. Direct p-regulation of pro-inflammatory cytokines as IL-1β, TNF-α, IL-10, TLR3, and INF-α, INFγ1 was observed after stimulation of carp head kidney (HK) cells with allicin extract. These results strongly indicate that allicin is responsible for the anti-inflammatory effects. Further, the results suggest that there are potential therapeutic effects of allicin on chronic inflammatory diseases. These effects need more investigations in aquaculture industries.</p>

scholarly journals Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 169 ◽  
Author(s):  
Ray K. Boyapati ◽  
Arina Tamborska ◽  
David A. Dorward ◽  
Gwo-Tzer Ho
Keyword(s):  
Mitochondrial Dna ◽  
Lupus Erythematosus ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Pathogenic Factor ◽  
Danger Signal ◽  
Bacterial Dna ◽  
Mitochondrial Homeostasis ◽  
Organ Specific

Mitochondrial DNA (mtDNA) has many similarities with bacterial DNA because of their shared common ancestry. Increasing evidence demonstrates mtDNA to be a potent danger signal that is recognised by the innate immune system and can directly modulate the inflammatory response. In humans, elevated circulating mtDNA is found in conditions with significant tissue injury such as trauma and sepsis and increasingly in chronic organ-specific and systemic illnesses such as steatohepatitis and systemic lupus erythematosus. In this review, we examine our current understanding of mtDNA-mediated inflammation and how the mechanisms regulating mitochondrial homeostasis and mtDNA release represent exciting and previously under-recognised important factors in many human inflammatory diseases, offering many new translational opportunities.

scholarly journals Glycomacropeptide Bioactivity and Health: A Review Highlighting Action Mechanisms and Signaling Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 598 ◽  
Author(s):  
Laura Córdova-Dávalos ◽  
Mariela Jiménez ◽  
Eva Salinas
Keyword(s):  
Signaling Pathways ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Action Mechanisms ◽  
Comprehensive Compilation

Food-derived bioactive peptides are reported as beneficial and safe for human health. Glycomacropeptide (GMP) is a milk-protein-derived peptide that, in addition to its nutritional value, retains many biological properties and has therapeutic effects in several inflammatory disorders. GMP was shown under in vitro and in vivo conditions to exert a number of activities that regulate the physiology of important body systems, namely the gastrointestinal, endocrine, and immune systems. This review represents a comprehensive compilation summarizing the current knowledge and updated information on the major biological properties associated with GMP. GMP bioactivity is addressed with special attention on mechanisms of action, signaling pathways involved, and structural characteristics implicated. In addition, the results of various studies dealing with the effects of GMP on models of inflammatory diseases are reviewed and discussed.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis

2021 ◽  
Vol 22 (15) ◽  
pp. 7960
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Jing-Long Huang ◽  
Jenn-Haung Lai
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Macrophage Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Inflammatory Joint Diseases ◽  
Tissue Repair And Regeneration ◽  
Related Cell ◽  
Key Players

Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and regeneration. Juvenile idiopathic arthritis (JIA) is an umbrella term describing inflammatory joint diseases in children. Accumulated evidence suggests a link between Mo and Mφ activation and JIA pathogenesis. Accordingly, topics regarding the signals and mechanisms regulating Mo and Mφ activation leading to pathologies in patients with JIA are of great interest. In this review, we critically summarize recent advances in the understanding of how Mo and Mφ activation is involved in JIA pathogenesis and focus on the signaling pathways and mechanisms participating in the related cell activation processes.

scholarly journals Isookanin Inhibits PGE2-Mediated Angiogenesis by Inducing Cell Arrest through Inhibiting the Phosphorylation of ERK1/2 and CREB in HMEC-1 Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6466
Author(s):  
Yingji Xin ◽  
Kyungbaeg Roh ◽  
Eunae Cho ◽  
Deokhoon Park ◽  
Wankyunn Whang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Diseases ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Potential Candidate ◽  
Creb Phosphorylation ◽  
Microvascular Endothelial ◽  
Cell Arrest

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

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