scholarly journals The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Se Eun Byeon ◽  
Young-Su Yi ◽  
Jueun Oh ◽  
Byong Chul Yoo ◽  
Sungyoul Hong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Src Kinase ◽  
Multiple Roles ◽  
Cellular Migration ◽  
Pharmaceutical Drugs ◽  
Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals The Pivotal Role of TBK1 in Inflammatory Responses Mediated by Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Tao Yu ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Jueun Oh ◽  
Deok Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Damage ◽  
Critical Role ◽  
Biological Response ◽  
Antiviral Defense ◽  
Functional Roles ◽  
Virus Interaction

Inflammation is a complex biological response of tissues to harmful stimuli such as pathogens, cell damage, or irritants. Inflammation is considered to be a major cause of most chronic diseases, especially in more than 100 types of inflammatory diseases which include Alzheimer's disease, rheumatoid arthritis, asthma, atherosclerosis, Crohn's disease, colitis, dermatitis, hepatitis, and Parkinson's disease. Recently, an increasing number of studies have focused on inflammatory diseases. TBK1 is a serine/threonine-protein kinase which regulates antiviral defense, host-virus interaction, and immunity. It is ubiquitously expressed in mouse stomach, colon, thymus, and liver. Interestingly, high levels of active TBK1 have also been found to be associated with inflammatory diseases, indicating that TBK1 is closely related to inflammatory responses. Even though relatively few studies have addressed the functional roles of TBK1 relating to inflammation, this paper discusses some recent findings that support the critical role of TBK1 in inflammatory diseases and underlie the necessity of trials to develop useful remedies or therapeutics that target TBK1 for the treatment of inflammatory diseases.

scholarly journals Herbal Plants: The Role of AhR in Mediating Immunomodulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Izzah Bungsu ◽  
Nurolaini Kifli ◽  
Siti Rohaiza Ahmad ◽  
Hazim Ghani ◽  
Anne Catherine Cunningham
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategy ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Aryl Hydrocarbon ◽  
Herbal Plants ◽  
Inflammatory Bowel ◽  
Cellular Immune

The prevalence of chronic inflammatory diseases including inflammatory bowel disease (IBD), autoimmunity and cancer have increased in recent years. Herbal-based compounds such as flavonoids have been demonstrated to contribute to the modulation of these diseases although understanding their mechanism of action remains limited. Flavonoids are able to interact with cellular immune components in a distinct way and influence immune responses at a molecular level. In this mini review, we highlight recent progress in our understanding of the modulation of immune responses by the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor whose activity can be regulated by diverse molecules including flavonoids. We focus on the role of AhR in integrating signals from flavonoids to modulate inflammatory responses using in vitro and experimental animal models. We also summarize the limitations of these studies. Medicinal herbs have been widely used to treat inflammatory disorders and may offer a valuable therapeutic strategy to treat aberrant inflammatory responses by modulation of the AhR pathway.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

scholarly journals Insights in the Role of Lipids, Oxidative Stress and Inflammation in Rheumatoid Arthritis Unveiled by New Trends in Lipidomic Investigations

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 45
Author(s):  
Helena Beatriz Ferreira ◽  
Tânia Melo ◽  
Artur Paiva ◽  
Maria do Rosário Domingues
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lipid Profile ◽  
Inflammatory Responses ◽  
Molecular Level ◽  
Lipid Hydroperoxides ◽  
Lipid Species ◽  
Inflammatory Autoimmune Disease

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.

Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective

2021 ◽  
Author(s):  
Denisse Vega Ocasio ◽  
Anna M. Stewart-Ibarra ◽  
Rachel Sippy ◽  
Christina Li ◽  
Kaitlyn McCue ◽  
...  
Keyword(s):  
At Risk ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Social Stressors ◽  
Biological Responses ◽  
Distress Symptoms ◽  
Tnf Α ◽  
Hair Samples ◽  
Arboviral Diseases

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-β. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

scholarly journals Role of Microbiome in Rheumatic Diseases

2017 ◽  
Vol 17 (2) ◽  
pp. 58-63 ◽  
Author(s):  
Chi Kit Au ◽  
Tin Lok Lai ◽  
Cheuk Wan Yim
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Rheumatic Diseases ◽  
Pivotal Role ◽  
Human Gut ◽  
Future Role ◽  
Human Gut Microbiota ◽  
Rheumatic Manifestations

AbstractMajority of rheumatic diseases are complex and multifactorial in etiology. Emerging studies has suggested that the change of human microbiota, especially in the gut, play a pivotal role in its pathogenesis. Dysequilibrium of the gut microbiota triggers the imbalance between pro- and anti- inflammatory immune responses and results in different rheumatic manifestations, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). In this article, current and future role of the human gut microbiota in rheumatic diseases are discussed.

scholarly journals Immunosuppressive Mechanisms of Regulatory B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Regulatory B Cells ◽  
Cell Surface Proteins ◽  
The Past ◽  
And Function

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

scholarly journals Prostaglandins and Rheumatoid Arthritis

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammad Javad Fattahi ◽  
Abbas Mirshafiey
Keyword(s):  
Rheumatoid Arthritis ◽  
Arachidonic Acid ◽  
Immune Responses ◽  
Cartilage Destruction ◽  
Heterogeneous Population ◽  
Therapeutic Protocol ◽  
Site Of Action ◽  
And Cartilage ◽  
Homeostatic Mechanisms

Rheumatoid arthritis (RA) is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs). Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

Abstract 19409: β2-Adrenergic Receptor Regulation of Innate Immune Responses Following Acute Myocardial Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Laurel A Grisanti ◽  
Anna Gumpert ◽  
Joshua Gorsky ◽  
Ashley A Repas ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adrenergic Receptor ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Cellular Migration ◽  
Chimeric Mouse ◽  
Ccr2 Expression ◽  
Β2 Adrenergic Receptor ◽  
The Impact

Inflammatory responses are important for cardiac remodeling and tissue repair after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune responses, in large part through the β2-adrenergic receptor (β2AR), however the influence of β2AR in regulating the inflammatory response following MI is unknown. Thus, to examine the contribution of β2AR on immune cells following MI, wild-type (WT) mice were irradiated and then received β2ARKO or WT control bone marrow (BM) transplants to create immune cell-specific knockout (KO) animals. Lack of β2AR expression in BM resulted in 100% mortality from cardiac rupture within two weeks of receiving MI, in contrast to their WT counterparts that had ∼20% death. Granulocyte populations were sequestered in the spleen of β2ARKO chimeric mice resulting in reductions in post-MI infiltration of monocyte/macrophage, neutrophil and mast cell populations into the heart. Additionally, alterations in chemokine receptor levels, particularly CCR2, on BM resulted in decreased cellular migration, and use of a CCR2 antagonist in vivo recapitulated the β2ARKO chimeric mouse phenotype following MI. Administration of β2AR agonists in vitro and in vivo increased CCR2 expression and BM migration while β2AR antagonists decreased CCR2 expression and increased splenic leukocyte retention in vivo . Use of pepducins as allosteric modulators of β2AR signaling demonstrated the importance of β-arrestin-mediated signaling in increasing CCR2 expression and responses. The impact of β2AR deletion on BM cell CCR2 expression and migration, splenic retention of leukocytes and reciprocal cardiac leukocyte infiltration following MI could be reversed via lentivirus-mediated β2AR rescue in the β2ARKO BM prior to transplantation. These results demonstrate the critical role of β2AR in the regulation of CCR2 expression on hematopoietic cells and its importance in mounting an immune response to promote healing following acute cardiac injury.

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