scholarly journals The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas

2021 ◽  
Vol 34 ◽  
Author(s):  
Gokçen TELLI ◽  
Inci KAZKAYASI ◽  
Serdar UMA
Keyword(s):  
Oral Absorption ◽  
Inflammatory Diseases ◽  
Food Supplement ◽  
Peripheral Inflammation ◽  
Independent Manner ◽  
Inflammatory Conditions ◽  
Paw Oedema ◽  
Serotonin Biosynthesis ◽  
Oral Doses

ABSTRACT Objective 5-Hydroxytryptophan is the precursor compound of serotonin biosynthesis. The oral absorption of 5-Hydroxytryptophan is close to 100% and, unlike serotonin, it crosses the blood-brain barrier freely. 5-Hydroxytryptophan has been used as a food supplement for many years to treat anxiety and depression. Recent studies have shown that 5-Hydroxytryptophan suppresses the pro-inflammatory mediators and is effective in some inflammatory diseases, such as arthritis and allergic asthma. However, the role of 5-Hydroxytryptophan supplements on acute peripheral inflammation has not been investigated yet. In this study, the in vivo anti-inflammatory activity of 5-Hydroxytryptophan was evaluated with a carrageenan-induced paw oedema test in mice. Methods For the investigation of the acute antiinflammatory activity, single oral doses of 5-Hydroxytryptophan (1.5, 5 and 20mg/kg) were given to mice 1.5 hours prior to the carrageenan test. For chronic activity, the same oral doses were administered daily for two weeks prior to the carrageenan test on the 14th day. To induce inflammation, 0.01mL of 2% carrageenan was injected into the paws of mice. Results Supplementation with 5-Hydroxytryptophan significantly reduced inflammation in a dose-independent manner which was irrespective of the duration of exposure (per cent inhibition in acute experiments was 35.4%, 20.9%, 24.0%, and per cent inhibition in chronic experiments was 29.5%, 35.3%, 40.8% for the doses of 1.5, 5, and 20mg/kg, respectively). Conclusion Our findings demonstrate for the first time that 5-HTP supplements have the potential of suppressing the measures of acute peripheral inflammation. It is suggested that, apart from several diseases where serotonin is believed to play an important role, including depression, patients with inflammatory conditions may also benefit from 5-HTP.

scholarly journals Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils

2004 ◽  
Vol 199 (10) ◽  
pp. 1343-1354 ◽  
Author(s):  
Frank Altznauer ◽  
Sibylla Martinelli ◽  
Shida Yousefi ◽  
Christine Thürig ◽  
Inès Schmid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Inflammatory Diseases ◽  
Survivin Expression ◽  
Current View ◽  
Proliferating Cells ◽  
Independent Manner ◽  
Inflammatory Conditions ◽  
Apoptosis Protein

Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.

scholarly journals Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1

2006 ◽  
Vol 203 (8) ◽  
pp. 1883-1889 ◽  
Author(s):  
Sonya M. Abraham ◽  
Toby Lawrence ◽  
Anna Kleiman ◽  
Paul Warden ◽  
Mino Medghalchi ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Independent Manner ◽  
Antiinflammatory Action ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Mouse Macrophages ◽  
Antiinflammatory Effects

Glucocorticoids (GCs), which are used in the treatment of immune-mediated inflammatory diseases, inhibit the expression of many inflammatory mediators. They can also induce the expression of dual specificity phosphatase 1 (DUSP1; otherwise known as mitogen-activated protein kinase [MAPK] phosphatase 1), which dephosphorylates and inactivates MAPKs. We investigated the role of DUSP1 in the antiinflammatory action of the GC dexamethasone (Dex). Dex-mediated inhibition of c-Jun N-terminal kinase and p38 MAPK was abrogated in DUSP1−/− mouse macrophages. Dex-mediated suppression of several proinflammatory genes (including tumor necrosis factor, cyclooxygenase 2, and interleukin 1α and 1β) was impaired in DUSP1−/− mouse macrophages, whereas other proinflammatory genes were inhibited by Dex in a DUSP1-independent manner. In vivo antiinflammatory effects of Dex on zymosan-induced inflammation were impaired in DUSP1−/− mice. Therefore, the expression of DUSP1 is required for the inhibition of proinflammatory signaling pathways by Dex in mouse macrophages. Furthermore, DUSP1 contributes to the antiinflammatory effects of Dex in vitro and in vivo.

scholarly journals Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide

2016 ◽  
Vol 13 (122) ◽  
pp. 20160539 ◽  
Author(s):  
Etheresia Pretorius ◽  
Sthembile Mbotwe ◽  
Janette Bester ◽  
Christopher J. Robinson ◽  
Douglas B. Kell
Keyword(s):  
Inflammatory Diseases ◽  
Isothermal Calorimetry ◽  
Amyloid Β ◽  
Bacterial Lipopolysaccharide ◽  
Primary Role ◽  
Inflammatory Conditions ◽  
Healthy Donors ◽  
Mechanistic Analysis ◽  
Amyloid Diseases

It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been tested directly. Here, we show that the addition of tiny concentrations (0.2 ng l −1 ) of bacterial LPS to both whole blood and platelet-poor plasma of normal, healthy donors leads to marked changes in the nature of the fibrin fibres so formed, as observed by ultrastructural and fluorescence microscopy (the latter implying that the fibrin is actually in an amyloid β-sheet-rich form that on stoichiometric grounds must occur autocatalytically). They resemble those seen in a number of inflammatory (and also amyloid) diseases, consistent with an involvement of LPS in their aetiology. These changes are mirrored by changes in their viscoelastic properties as measured by thromboelastography. As the terminal stages of coagulation involve the polymerization of fibrinogen into fibrin fibres, we tested whether LPS would bind to fibrinogen directly. We demonstrated this using isothermal calorimetry. Finally, we show that these changes in fibre structure are mirrored when the experiment is done simply with purified fibrinogen and thrombin (±0.2 ng l −1 LPS). This ratio of concentrations of LPS : fibrinogen in vivo represents a molecular amplification by the LPS of more than 10 8 -fold, a number that is probably unparalleled in biology. The observation of a direct effect of such highly substoichiometric amounts of LPS on both fibrinogen and coagulation can account for the role of very small numbers of dormant bacteria in disease progression in a great many inflammatory conditions, and opens up this process to further mechanistic analysis and possible treatment.

scholarly journals Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Anupama Karnam ◽  
Naresh Rambabu ◽  
Mrinmoy Das ◽  
Melissa Bou-Jaoudeh ◽  
Sandrine Delignat ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intravenous Immunoglobulin ◽  
Inflammatory Diseases ◽  
Central Component ◽  
Independent Manner ◽  
Reciprocal Regulation ◽  
Autoimmune And Inflammatory Diseases ◽  
Anti Inflammatory

AbstractTherapeutic normal IgG intravenous immunoglobulin (IVIG) is a well-established first-line immunotherapy for many autoimmune and inflammatory diseases. Though several mechanisms have been proposed for the anti-inflammatory actions of IVIG, associated signaling pathways are not well studied. As β-catenin, the central component of the canonical Wnt pathway, plays an important role in imparting tolerogenic properties to dendritic cells (DCs) and in reducing inflammation, we explored whether IVIG induces the β-catenin pathway to exert anti-inflammatory effects. We show that IVIG in an IgG-sialylation independent manner activates β-catenin in human DCs along with upregulation of Wnt5a secretion. Mechanistically, β-catenin activation by IVIG requires intact IgG and LRP5/6 co-receptors, but FcγRIIA and Syk are not implicated. Despite induction of β-catenin, this pathway is dispensable for anti-inflammatory actions of IVIG in vitro and for mediating the protection against experimental autoimmune encephalomyelitis in vivo in mice, and reciprocal regulation of effector Th17/Th1 and regulatory T cells.

scholarly journals Essential Oils and Their Major Compounds in the Treatment of Chronic Inflammation: A Review of Antioxidant Potential in Preclinical Studies and Molecular Mechanisms

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Érica Martins de Lavor ◽  
Antônio Wilton Cavalcante Fernandes ◽  
Roxana Braga de Andrade Teles ◽  
Ana Ediléia Barbosa Pereira Leal ◽  
Raimundo Gonçalves de Oliveira Júnior ◽  
...  
Keyword(s):  
Essential Oils ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Biologically Active ◽  
Preclinical Studies ◽  
Inflammatory Conditions ◽  
Potential Activity

Inflammatory diseases result from the body’s response to tissue damage, and if the resolution is not adequate or the stimulus persists, there will be progression from acute inflammation to chronic inflammation, leading to the development of cancer and neurodegenerative and autoimmune diseases. Due to the complexity of events that occur in inflammation associated with the adverse effects of drugs used in clinical practice, it is necessary to search for new biologically active compounds with anti-inflammatory activity. Among natural products, essential oils (EOs) present promising results in preclinical studies, with action in the main mechanisms involved in the pathology of inflammation. The present systematic review summarizes the pharmacological effects of EOs and their compounds in in vitro and in vivo models for inflammation. The research was conducted in the following databases: PubMed, Scopus, BIREME, Scielo, Open Grey, and Science Direct. Based on the inclusion criteria, 30 articles were selected and discussed in this review. The studies listed revealed a potential activity of EOs and their compounds for the treatment of inflammatory diseases, especially in chronic inflammatory conditions, with the main mechanism involving reduction of reactive oxygen and nitrogen species associated with an elevation of antioxidant enzymes as well as the reduction of the nuclear factor kappa B (NF-κB), reducing the expression of proinflammatory cytokines. Thus, this review suggests that EOs and their major compounds are promising tools for the treatment of chronic inflammation.

scholarly journals Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kangfeng Jiang ◽  
Weiqi Ye ◽  
Qian Bai ◽  
Jinyin Cai ◽  
Haichong Wu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Lipoteichoic Acid ◽  
In Vivo Studies ◽  
Economic Losses ◽  
Inflammatory Conditions ◽  
Wide Range

Staphylococcus aureus (S. aureus), a notorious pathogenic bacterium prevalent in the environment, causes a wide range of inflammatory diseases such as endometritis. Endometritis is an inflammatory disease in humans and mammals, which prolongs uterine involution and causes great economic losses. MiR-30a plays an importan trole in the process of inflammation; however, the regulatory role of miR-30a in endometritis is still unknown. Here, we first noticed that there was an increased level of miR-30a in uterine samples of cows with endometritis. And then, bovine endometrial epithelial (BEND) cells stimulated with the virulence factor lipoteichoic acid (LTA) from S. aureus were used as an in vitro endometritis model to explore the potential role of miR-30a in the pathogenesis of endometritis. Our data showed that the induction of the miR-30a expression is dependent on NF-κB activation, and its overexpression significantly decreased the levels of IL-1β and IL-6. Furthermore, we observed that the overexpression of miR-30a inhibited its translation by binding to 3 ′ − UTR of MyD88 mRNA, thus preventing the activation of Nox2 and NF-κB and ROS accumulation. Meanwhile, in vivo studies further revealed that upregulation of miR-30a using chemically synthesized agomirs alleviates the inflammatory conditions in an experimental mouse model of endometritis, as indicated by inhibition of ROS and NF-κB. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis.

scholarly journals MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation

2016 ◽  
Vol 113 (23) ◽  
pp. 6526-6531 ◽  
Author(s):  
Bishuang Cai ◽  
Edward B. Thorp ◽  
Amanda C. Doran ◽  
Manikandan Subramanian ◽  
Brian E. Sansbury ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
Genetically Engineered ◽  
Sterile Inflammation ◽  
Long Chain Fatty Acid ◽  
Inflammatory Conditions ◽  
Remote Organ ◽  
Inflammation Resolution

The acute inflammatory response requires a coordinated resolution program to prevent excessive inflammation, repair collateral damage, and restore tissue homeostasis, and failure of this response contributes to the pathology of numerous chronic inflammatory diseases. Resolution is mediated in part by long-chain fatty acid-derived lipid mediators called specialized proresolving mediators (SPMs). However, how SPMs are regulated during the inflammatory response, and how this process goes awry in inflammatory diseases, are poorly understood. We now show that signaling through the Mer proto-oncogene tyrosine kinase (MerTK) receptor in cultured macrophages and in sterile inflammation in vivo promotes SPM biosynthesis by a mechanism involving an increase in the cytoplasmic:nuclear ratio of a key SPM biosynthetic enzyme, 5-lipoxygenase. This action of MerTK is linked to the resolution of sterile peritonitis and, after ischemia–reperfusion (I/R) injury, to increased circulating SPMs and decreased remote organ inflammation. MerTK is susceptible to ADAM metallopeptidase domain 17 (ADAM17)-mediated cell-surface cleavage under inflammatory conditions, but the functional significance is not known. We show here that SPM biosynthesis is increased and inflammation resolution is improved in a new mouse model in which endogenous MerTK was replaced with a genetically engineered variant that is cleavage-resistant (MertkCR). MertkCR mice also have increased circulating levels of SPMs and less lung injury after I/R. Thus, MerTK cleavage during inflammation limits SPM biosynthesis and the resolution response. These findings contribute to our understanding of how SPM synthesis is regulated during the inflammatory response and suggest new therapeutic avenues to boost resolution in settings where defective resolution promotes disease progression.

scholarly journals Thawed Mesenchymal Stem Cell Product Shows Comparable Immunomodulatory Potency to Cultured Cells In Vitro and in Polymicrobial Septic Animals

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuan Tan ◽  
Mahmoud Salkhordeh ◽  
Jia-Pey Wang ◽  
Andrea McRae ◽  
Luciana Souza-Moreira ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Inflammatory Diseases ◽  
Endothelial Permeability ◽  
Innate Immune ◽  
Activated T Cells ◽  
Inflammatory Conditions ◽  
Significant Difference ◽  
Stem Cell Product

AbstractMesenchymal stem cells (MSCs) have been shown to exert immunomodulatory effects in both acute and chronic diseases. In acute inflammatory conditions like sepsis, cell therapy must be administered within hours of diagnosis, requiring “off-the-shelf” cryopreserved allogeneic cell products. However, their immunomodulatory potency, particularly in abilities to modulate innate immune cells, has not been well documented. Herein we compared the stabilities and functionalities of cultured versus thawed, donor-matched MSCs in modulating immune responses in vitro and in vivo. Cultured and thawed MSCs exhibited similar surface marker profiles and viabilities at 0 hr; however, thawed MSCs exhibited higher levels of apoptotic cells beyond 4 hrs. In vitro potency assays showed no significant difference between the abilities of both MSCs (donor-matched) to suppress proliferation of activated T cells, enhance phagocytosis of monocytes, and restore endothelial permeability after injury. Most importantly, in animals with polymicrobial sepsis, both MSCs significantly improved the phagocytic ability of peritoneal lavage cells, and reduced plasma levels of lactate and selected inflammatory cytokines without significant difference between groups. These results show comparable in vitro and in vivo immunomodulatory efficacy of thawed and fresh MSC products, providing further evidence for the utility of a cryopreserved MSC product for acute inflammatory diseases.

scholarly journals Neutrophils preferentially phagocytose elongated particles—An opportunity for selective targeting in acute inflammatory diseases

2020 ◽  
Vol 6 (24) ◽  
pp. eaba1474 ◽  
Author(s):  
Hanieh Safari ◽  
William J. Kelley ◽  
Eiji Saito ◽  
Nicholas Kaczorowski ◽  
Lauren Carethers ◽  
...  
Keyword(s):  
Particle Shape ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Specific Interaction ◽  
Mononuclear Phagocytes ◽  
Human Neutrophils ◽  
Inflammatory Conditions ◽  
Polymeric Particles ◽  
Physical Particle

Polymeric particles have recently been used to modulate the behavior of immune cells in the treatment of various inflammatory conditions. However, there is little understanding of how physical particle parameters affect their specific interaction with different leukocyte subtypes. While particle shape is known to be a crucial factor in their phagocytosis by macrophages, where elongated particles are reported to experience reduced uptake, it remains unclear how shape influences phagocytosis by circulating phagocytes, including neutrophils that are the most abundant leukocyte in human blood. In this study, we investigated the phagocytosis of rod-shaped polymeric particles by human neutrophils relative to other leukocytes. In contrast to macrophages and other mononuclear phagocytes, neutrophils were found to exhibit increased internalization of rods in ex vivo and in vivo experimentation. This result suggests that alteration of particle shape can be used to selectively target neutrophils in inflammatory pathologies where these cells play a substantial role.

scholarly journals Cannabinoids in the Pathophysiology of Skin Inflammation

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 652 ◽  
Author(s):  
Cristian Scheau ◽  
Ioana Anca Badarau ◽  
Livia-Gratiela Mihai ◽  
Andreea-Elena Scheau ◽  
Daniel Octavian Costache ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Synthetic Cannabinoids ◽  
Skin Inflammation ◽  
Cellular Mechanisms ◽  
Inflammatory Conditions ◽  
Early Results ◽  
Inflammatory Component

Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

Sign in / Sign up

Export Citation Format

Share Document