scholarly journals Modulating toll-like receptor-mediated inflammatory responses following exposure of whole cell and lipopolysaccharide component from Porphyromonas gingivalis in wistar rat models

2017 ◽  
Vol 11 (04) ◽  
pp. 422-426 ◽  
Author(s):  
Sindy Cornelia Nelwan ◽  
Ricardo Adrian Nugraha ◽  
Anang Endaryanto ◽  
Indrawati Retno
Keyword(s):  
Statistical Analysis ◽  
Inflammatory Response ◽  
Porphyromonas Gingivalis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Wistar Rat ◽  
Vital Role ◽  
Toll Like Receptor ◽  
Whole Cell ◽  
Significant Difference

ABSTRACT Objective: To explore host innate inflammatory response and the signal pathway induced by Porphyromonas gingivalis by measuring level of toll-like receptor 2 (TLR2) and TLR4 activity. Materials and Methods: Animal experimental study with pretest-posttest controlled group design were done between January 1 and December 10, 2016. . Total of 28 wistar rats had been used, randomized into 7 groups, each were given various dose of intra-sulcural injection of Porphyromonas gingivalis lipopolysaccharide. Statistical Analysis: Normality were measured by Shapiro–Wilk test, while statistical analysis made by ANOVA, t test, Pearson, and linear regression model.. Results: At day 0, no significant difference TLR2 and TLR4 level were measured. At day 4, there is a slight difference between TLR2 and TLR4 level in each group. At day 11, there is a significant difference between TLR2 and TLR4 level in each group. Group with exposure of whole cell will develop greater TLR2 but lower TLR4 level. In the contrary, group with exposure of LPS will develop greater TLR4 but lower TLR2 level. Conclusion: Our data supported that P. gingivalis played a vital role in the pathogenesis of pathogen-induced inflammatory responses in which TLR2 and TLR4 have different molecular mechanisms following recognition of pathogens and inflammatory response.

scholarly journals Unfulfilled Inflammatory Resolution: A Key Factor in the Pathogenesis of Psoriasis

2020 ◽  
Author(s):  
Zohreh Jadali
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Relevant Literature ◽  
Regulatory Mechanisms ◽  
Immune Mediated ◽  
Key Factor ◽  
Inflammation Resolution

Recent literature has highlighted the importance of chronic inflammation in psoriasis pathogenesis. Non-resolving inflammation can trigger progressive tissue damage and inflammatory mediator release which in turn perpetuate the inflammatory cycle. Under normal conditions, inflammatory responses are tightly controlled through several mechanisms that restore normal tissue function and structure. Defects in regulatory mechanisms of the inflammatory response can result in persistent unresolved inflammation and further increases of inflammation. Therefore, this review focuses on defects in regulatory mechanisms of inflammatory responses that lead to uncontrolled chronic inflammation in psoriasis. Databases such as Pubmed Embase, ISI, and Iranian databases including Iranmedex, and SID were researched to identify relevant literature. The results of this review indicate that dysregulation of the inflammatory response may be a likely cause of various immune-mediated inflammatory disorders such as psoriasis. Based on current findings, advances in understanding the cellular and molecular mechanisms involved in inflammation resolution are not only improving our knowledge of the pathogenesis of chronic inflammatory diseases but also supporting the development of new therapeutic strategies.

scholarly journals Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4

2020 ◽  
Vol 7 ◽  
Author(s):  
Zheng Xiao ◽  
Bin Kong ◽  
Hongjie Yang ◽  
Chang Dai ◽  
Jin Fang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cardiac Hypertrophy ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Immune Cell ◽  
Current Knowledge ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling

Toll-like receptor 4 (TLR4), a key pattern recognition receptor, initiates the innate immune response and leads to chronic and acute inflammation. In the past decades, accumulating evidence has implicated TLR4-mediated inflammatory response in regulation of myocardium hypertrophic remodeling, indicating that regulation of the TLR4 signaling pathway may be an effective strategy for managing cardiac hypertrophy's pathophysiology. Given TLR4's significance, it is imperative to review the molecular mechanisms and roles underlying TLR4 signaling in cardiac hypertrophy. Here, we comprehensively review the current knowledge of TLR4-mediated inflammatory response and its interaction ligands and co-receptors, as well as activation of various intracellular signaling. We also describe the associated roles in promoting immune cell infiltration and inflammatory mediator secretion, that ultimately cause cardiac hypertrophy. Finally, we provide examples of some of the most promising drugs and new technologies that have the potential to attenuate TLR4-mediated inflammatory response and prevent or reverse the ominous cardiac hypertrophy outcomes.

scholarly journals Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes

2020 ◽  
Vol 21 (10) ◽  
pp. 3446 ◽  
Author(s):  
Jung-Won Shin ◽  
Hyun-Sun Lee ◽  
Jung-Im Na ◽  
Chang-Hun Huh ◽  
Kyung-Chan Park ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Antioxidant Properties ◽  
Complex Mixture ◽  
Human Keratinocytes ◽  
Receptor Activation ◽  
Air Pollutant ◽  
Cellular Inflammatory Response

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol’s effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.

scholarly journals Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

2021 ◽  
Vol 8 ◽  
Author(s):  
Yufei Xie ◽  
Annemarie H. Meijer ◽  
Marcel J. M. Schaaf
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Model Systems ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

scholarly journals TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin

2020 ◽  
Vol 117 (43) ◽  
pp. 26895-26906
Author(s):  
Lee Swanson ◽  
Gajanan D. Katkar ◽  
Julian Tam ◽  
Rama F. Pranadinata ◽  
Yogitha Chareddy ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Sodium Sulfate ◽  
Inflammatory Responses ◽  
Transcriptional Response ◽  
Fine Tuning ◽  
Specific Gene ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Receptor Dimerization

Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV (a.k.a. Girdin), titrates such inflammatory response in macrophages. Upon challenge with either live microbes or microbe-derived lipopolysaccharides (a ligand for TLR4), macrophages with GIV mount a more tolerant (hypo-reactive) transcriptional response and suppress proinflammatory cytokines and signaling pathways (i.e., NFkB and CREB) downstream of TLR4 compared to their GIV-depleted counterparts. Myeloid-specific gene-depletion studies confirmed that the presence of GIV ameliorates dextran sodium sulfate-induced colitis and sepsis-induced death. The antiinflammatory actions of GIV are mediated via its C-terminally located TIR-like BB-loop (TILL) motif which binds the cytoplasmic TIR modules of TLR4 in a manner that precludes receptor dimerization; such dimerization is a prerequisite for proinflammatory signaling. Binding of GIV’s TILL motif to TIR modules inhibits proinflammatory signaling via other TLRs, suggesting a convergent paradigm for fine-tuning macrophage inflammatory responses.

Abstract 189: The Role of Spleen Tyrosine Kinase, Syk, in CD36-Toll Like Receptor Cooperative Signaling in Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Tathagat Dutta Ray ◽  
Bhama Ramkhelawon ◽  
Kathryn J Moore
Keyword(s):  
Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Sh2 Domain ◽  
Sterile Inflammation ◽  
Toll Like Receptor ◽  
Spleen Tyrosine Kinase

Atherosclerosis is characterized by chronic sterile inflammation of the artery wall in which cells of the monocyte lineage accumulate in response to the deposition of low density lipoprotein (LDL). We previously established that recognition of oxidized LDL (oxLDL) by CD36 triggers assembly of a novel Toll-like receptor heterodimer composed of TLR4 and TLR6. Here we set out to understand the molecular mechanisms of CD36/TLR4/TLR6 activation and establish how it triggers downstream signals that lead to the expression of the pro-inflammatory mediators that have been directly implicated in the deleterious effects of oxLDL and atherosclerosis progression. By confocal microscopy we demonstrate that oxLDL induces CD36, TLR4 and TLR6 co-localization in intracellular compartments, but not on the cell surface of macrophages. Notably, inhibition of oxLDL endocytosis (with Dynasore) or lysosomal maturation (with Bafilomycin A or NH4Cl) blocks CD36-TLR4-TLR6 complex formation and oxLDL-induced cytokine responses in macrophages. These data indicate that both ligand internalization and lysosomal acidification are required for assembly of a functional CD36/TLR4/TLR6 signaling complex. Notably, CD36 contains a hemi-ITIM motif in the C-terminus that is reported to interact with the spleen tyrosine kinase Syk through its SH2 domain. As Syk has recently been implicated in the trafficking of CD14 and TLR4 to the endosome in response to LPS, we investigated the role of this kinase in CD36/TLR4/TLR6 signaling. We find that Syk is required for CD36 internalization and TLR4/TLR6 heterodimerization. Using a pharmacological inhibitor, we show that inhibition of Syk activity blocks oxLDL-induced TLR4-TLR6 co-precipitation and abrogates macrophage expression of both MyD88- (IL-1b, CXCL1) and TRIF-dependent (CCL5) cytokines/chemokines. Together, our data are consistent with a key role for Syk in the trafficking of CD36 and oxLDL to the lysosome, where it coordinates the assembly of a functional TLR4-TLR6 heterodimer to initiate signaling. This model highlights the importance of CD36 as a co-receptor that orchestrates TLR4-TLR6 trafficking and assembly to initiate the detrimental inflammatory responses that promote the progression of atherosclerosis.

Role of medicinal plants against neurodegenerative diseases

2021 ◽  
Vol 22 ◽  
Author(s):  
Ritika Luthra ◽  
Arpita Roy
Keyword(s):  
Medicinal Plants ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Significant Loss ◽  
Therapeutic Interventions ◽  
Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

scholarly journals Reconciling the IPC and Two-Hit Models: Dissecting the Underlying Cellular and Molecular Mechanisms of Two Seemingly Opposing Frameworks

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Carlos F. M. Morris ◽  
Muhammad Tahir ◽  
Samina Arshid ◽  
Mariana S. Castro ◽  
Wagner Fontes
Keyword(s):  
Inflammatory Response ◽  
Clinical Outcomes ◽  
Ischemic Preconditioning ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Present Review ◽  
Host Responses ◽  
Ischemia And Reperfusion ◽  
Biological Models

Inflammatory cascades and mechanisms are ubiquitous during host responses to various types of insult. Biological models and interventional strategies have been devised as an effort to better understand and modulate inflammation-driven injuries. Amongst those the two-hit model stands as a plausible and intuitive framework that explains some of the most frequent clinical outcomes seen in injuries like trauma and sepsis. This model states that a first hit serves as a priming event upon which sequential insults can build on, culminating on maladaptive inflammatory responses. On a different front, ischemic preconditioning (IPC) has risen to light as a readily applicable tool for modulating the inflammatory response to ischemia and reperfusion. The idea is that mild ischemic insults, either remote or local, can cause organs and tissues to be more resilient to further ischemic insults. This seemingly contradictory role that the two models attribute to a first inflammatory hit, as priming in the former and protective in the latter, has set these two theories on opposing corners of the literature. The present review tries to reconcile both models by showing that, rather than debunking each other, each framework offers unique insights in understanding and modulating inflammation-related injuries.

scholarly journals Biocompatibility of acellular dermal matrix graft evaluated in culture of murine macrophages

2006 ◽  
Vol 14 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Ana Paula Vendramini ◽  
Rafaela Fernanda Melo ◽  
Rosemary Adriana Chiérici Marcantonio ◽  
Iracilda Zepone Carlos
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Statistical Analysis ◽  
Inflammatory Response ◽  
Acellular Dermal Matrix ◽  
Negative Control ◽  
Dermal Matrix ◽  
Murine Macrophages ◽  
Significant Difference ◽  
Acellular Dermal

The acellular dermal matrix allograft has been used as an alternative to autogenous palatal mucosal graft. The aim of this study was the evaluation of the biocompatibility of an acellular dermal matrix (AlloDerm®) in culture of macrophages. For hydrogen peroxidase determination we used the method of Pick & Kesari, and the Griess method for nitric oxide determination,. Statistical analysis showed no significant difference (p < 0,05) in the release of nitric oxide and hydrogen peroxide by the macrophages exposed to acellular dermal matrix and the negative control. The results suggest that acellular dermal matrix did not activate the cell inflammatory response.

In Vivo Comparison of the Inflammatory Response Induced by Different Vascular Biomaterials

Vascular ◽  
2005 ◽  
Vol 13 (4) ◽  
pp. 230-235 ◽  
Author(s):  
Steven J. Busuttil ◽  
Carla Drumm ◽  
Edward F. Plow
Keyword(s):  
Stainless Steel ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Disk Surface ◽  
The Other ◽  
Vascular Prostheses ◽  
Local Inflammatory Response ◽  
Macrophage Recruitment ◽  
Significant Difference

Biomaterial implants induce a local inflammatory response. A comparison of the inflammatory cell response was made between several biomaterials commonly used as vascular prostheses. Disks of polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), aluminum, titanium, copper, and stainless steel were surgically placed into the peritoneum of mice. Recruited macrophage and neutrophil populations were measured after recovery from the disk surface and peritoneal lavage. Following peritoneal biomaterial implants, there was no difference in total neutrophil or macrophage recruitment between mice implanted with PET, PTFE, aluminum, or titanium disks. However, there was significant attenuation of total neutrophil and macrophage recruitment to stainless steel compared with the other implants. Similarly, there was no significant difference in the percentage of leukocytes adherent to the PET, aluminum, or titanium disks. Macrophage adherence to the stainless steel disks was attenuated by 19.1%, and the number of neutrophils was attenuated by 69.1% when compared with PET implant mice. Mice implanted with copper disks universally expired. Leukocyte recruitment did not differ between PET, PTFE, aluminum, or titanium disks, suggesting that these materials stimulate similar inflammatory responses. Stainless steel disks recruited both fewer neutrophils and fewer macrophages and support lower adherence of these cells than the other biomaterials. Copper incited an overwhelming and fatal response.

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