Different Phases Of Inflammation Research Articles

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation

ObjectivesTo develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality...

Use of Poly Lactic-co-glycolic Acid Nano and Micro Particles in the Delivery of Drugs Modulating Different Phases of Inflammation.

Chronic inflammation contributes to the pathogenesis of many diseases, including apparently unrelated conditions such as metabolic disorders, cardiovascular diseases, neurodegenerative diseases, osteoporosis, and tumors, but the use of conventional anti-inflammatory drugs to treat these diseases is generally not very effective given their adverse effects. In addition, some alternative anti-inflammatory medications, such as many natural compounds, have scarce solubility and stability, which are associated with low bioavailability. Therefore, encapsulation within nanoparticles (NPs) may represent an effective strategy to enhance the pharmacological properties of these bioactive molecules, and poly lactic-co-glycolic acid (PLGA) NPs have been widely used because of their high biocompatibility and biodegradability and possibility to finely tune erosion time, hydrophilic/hydrophobic nature, and mechanical properties by acting on the polymer's composition and preparation technique. Many studies have been focused on the use of PLGA-NPs to deliver immunosuppressive treatments for autoimmune and allergic diseases or to elicit protective immune responses, such as in vaccination and cancer immunotherapy. By contrast, this review is focused on the use of PLGA NPs in preclinical in vivo models of other diseases in which a key role is played by chronic inflammation or unbalance between the protective and reparative phases of inflammation, with a particular focus on intestinal bowel disease; cardiovascular, neurodegenerative, osteoarticular, and ocular diseases; and wound healing.

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study.

BACKGROUNDChronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIMTo investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODSA total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTSA positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR.CONCLUSIONIn pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.

Pyruvate targets cytosolic phospholipase A2 and resolves inflammation

Purpose: Numerous studies are indicative of the potent molecular interaction between the energy metabolic supply and different phases of inflammation. Pyruvate is a glycolytic metabolite used for energy production and macromolecule biosynthesis and is also a crucial interaction in multiple metabolic pathways. However, little is known about its effects on cytokine release as well as the molecular events involved. Hence, the current study aims to investigate the role and mechanism of pyruvate in resolving inflammation and to identify its binding partner.

Synthesis and Anti-inflammatory Activity of 7-Non-steroidal Anti-inflammatory Drugs Substituted Flavone

Aim: Inflammation shows an important character in illnesses such for example cardiovascular diseases, asthma, malignant and diabetes. Food can guidance different phases of inflammation and can have an important influence on numerous inflammatory illnesses. Increasing scientific suggestion has displayed that polyphenolic compounds, such as flavonoids, which are originate in vegetables, fruits, cocoa or legumes, can have antiinflammatory activity. Current researches prevent enzymes or transcription factors significant for regulatory intermediaries involved in inflammation. Flavonoids are also famous as effective antioxidants with the potential to weaken tissue injury or fibrosis. Subsequently, frequent studies in vivo and in vitro models shows that flavonoids have the prospective to prevent the beginning and development of inflammatory activity. Materials and Methods: In the present research work, a series of flavones merge with Non-steroidal Anti-Inflammatory Drugs were synthesized from resorcinol through Baker- Venkataraman Method, characterized and calculated there in vitro anti-inflammatory activity by protein denaturation technique. Results: The outcome is protein denaturation studies shown that the compound FS found to be most potent anti-inflammatory activity. The percentage inhibitions were 97.66%. Key words: Albumin Denaturation, Baker Venkataraman transformation, Cyclooxygenase, Flavone, NSAIDS.

Trichostatin A modulates the macrophage phenotype by enhancing autophagy to reduce inflammation during polymicrobial sepsis

Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.

MicroRNAs as Molecular Switches in Macrophage Activation.

The efficacy of macrophage- mediated inflammatory response relies on the coordinated expression of key factors, which expression is finely regulated at both transcriptional and post-transcriptional level. Several studies have provided compelling evidence that microRNAs play pivotal roles in modulating macrophage activation, polarization, tissue infiltration, and resolution of inflammation. In this review, we highlight the essential molecular mechanisms underlying the different phases of inflammation that are targeted by microRNAs to inhibit or accelerate restoration to tissue integrity and homeostasis. We further review the impact of microRNA-dependent regulation of tumor-associated macrophages and the relative implication for tumor biology.

Anti-hyperalgesia effect of nanchelating based nano particle, RAc1, can be mediated via liver hepcidin expression modulation during persistent inflammation

ObjectiveRheumatoid arthritis (RA) is a chronic systemic inflammatory disorder accompanied with hyperalgesia, edema and pain. At least 30% of the patients failed to respond to the available treatments and medications, which yet have a lot of serious adverse effects on patients. So, using novel technologies to produce more efficient medications is needed. According to the role of iron manipulation in inflammatory process, we have synthetized RAc1 nano particle, which contains zinc and has iron chelating property. In the present study, we evaluated RAc1 nano particle effects on hyperalgesia and liver hepcidin and serum IL-1β and TNF-α expression levels during acute and chronic phases of adjuvant-induced inflammation in male rats and compared its effects with Deferoxamine. Methods and materialsComplete Freund's adjuvant (CFA)-induced arthritis was caused by single subcutaneous injection of CFA into the rat's hind paw on day zero. RAc1 with 100, 200 and 400 ng/kg doses and deferoxamin with doses of 200 mg/kg after diluting in vehicles were administered daily (i.p.) during the 21 days of the study after CFA injection. Hyperalgesia, Edema, liver hepcidin and serum IL-1β and TNF-α expression levels were assessed on days 0, 7, 14 and 21 of the study. ResultsThe results of this study indicated the role of RAc1 nano particle administration in reducing paw edema, thermal hyperalgesia, and liver hepcidin and serum IL-1β and TNF-α expression even in comparison with Deferoxamine during different phases of inflammation caused by CFA. ConclusionIt seems that RAc1 nano particle exerts its immune modulatory effects by decreasing liver hepcidin expression and serum IL-1β and TNF-α levels.

Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation.

Macrophages manifest distinct phenotype according to the organs in which they reside. In addition, they flexibly switch their character in adaptation to the changing environment. However, the molecular basis that explains the conversion of the macrophage phenotype has so far been unexplored. We find that CD169+ macrophages change their phenotype by regulating the level of a transcription factor Maf both in vitro and in vivo in C57BL/6J mice. When CD169+ macrophages were exposed to bacterial components, they expressed an array of acute inflammatory response genes in Maf-dependent manner and simultaneously start to downregulate Maf. This Maf suppression is dependent on accelerated degradation through proteasome pathway and microRNA-mediated silencing. The downregulation of Maf unlocks the NF-E2-related factor 2-dominant, cytoprotective/antioxidative program in the same macrophages. The present study provides new insights into the previously unanswered question of how macrophages initiate proinflammatory responses while retaining their capacity to repair injured tissues during inflammation.

Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molecular and behavioral aspects of adjuvant-induced arthritis.

Neuroinflammation plays a crucial role in expression of symptoms of numerous autoimmune and neurodegenerative diseases such as pain during rheumatoid arthritis. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways have been strongly implicated in the generation of pathological pain states, particularly at central nervous system sites and induction of spinal neuroinflammatory symptoms. The wide ranges of research to define new therapeutic approaches, including neuroimmune-modulators like stem cells are in progress. Mesenchymal stem cells conditioned medium (MSC-CM) has anti-inflammatory factors which can regulate the immune responses. The aim of this study was to investigate the effect of administration of MSC-CM on behavioral, cellular and molecular aspects of adjuvant-induced arthritis in male Wistar rats. Complete Freund's adjuvant (CFA)-induced arthritis (AA) was caused by single subcutaneous injection of CFA into the rat's hind paw on day 0. MSC-CM was administered daily (i.p.) and during the 21 days of the study after injection. Hyperalgesia, Edema, Serum TNF-α levels and p38MAPK and NF-κB activities were assessed on days 0,7,14 and 21 of the study. The results of this study indicated the role of MSC-CM in reducing inflammatory symptoms, serum TNF-α levels and activity of intracellular signaling pathway factors during different phases of inflammation caused by CFA. It seems that MSC-CM treatment due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain during CFA-induced arthritis.

The epigenetic landscape of innate immunity

The inflammatory response is the first line of defense against infectious agents or tissue damage. Innate immune cells are the crucial effectors regulating the different phase of inflammation. Their ability to timely develop an immune response is tightly controlled by the interplay of transcriptional and epigenetic mechanisms. The immunological imprinting elicited by exposure to different concentrations and types of infectious agents determine the functional fate of immune cells, forming the basis of innate immune memory. In this review we highlight the best-characterized examples of gene reprogramming occurring during different phases of inflammation with particular emphasis on the epigenetic marks that determine the specificity of the immune response. We further review the potential of cutting edge experimental techniques that have recently helped to reveal the deep complexity of epigenetic regulation during the inflammatory response.

Exudate suction blister: a novel in vivo model of acute infllammation and resolution in humans. (CAM1P.145)

Abstract Resolution of acute inflammation is an active process and its dysregulation may contribute to chronic inflammatory disorders. While animal models have been used to study resolution their appropriateness has been questioned. We describe a novel model of resolving inflammation in humans triggered by intradermal injection of UV killed E. coli into the forearm of healthy volunteers (n=30). Inflammatory exudate was drawn into a skin blister induced by negative pressure applied over the injection site. Blister cells were analyzed by flow cytometry while the cell free exudates were assayed for cytokines. To study the different phases of inflammation, blisters were raised at multiple time points up to day 14 post-injection. Vascular response was monitored by laser doppler. Onset (8hr) was characterised by peak erythema and neutrophilia (HLA-DR-/CD16++). By 24hr, neutrophil numbers had fallen by 80% while CD14+ monocytes and CD1c+ dendritic cell numbers increased, indicating resolution. At 48hr blood flow declined along with mononuclear cell numbers. Lymphocytes (CD4+, CD8+ and CD56+ cells) dominated the site at day 3 and persisted up to day 14. Levels of TNF-α, IL-8 and IL-1β were maximal at 8hr, IFN-γ at 24hr. This safe and reproducible model allows, for the first time, exploration of cells and soluble mediators in parallel with the clinical signs of resolution in humans. Potential applications include testing the efficacy of novel anti-inflammatory and pro-resolving drugs.

Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.

Monocytes/macrophages are key players in all phases of physiological and pathological inflammation. To understanding the regulation of macrophage functional differentiation during inflammation, we designed an in vitro model that recapitulates the different phases of the reaction (recruitment, initiation, development, and resolution), based on human primary blood monocytes exposed to sequential changes in microenvironmental conditions. All reaction phases were profiled by transcriptomic microarray analysis. Distinct clusters of genes were identified that are differentially regulated through the different phases of inflammation. The gene sets defined by GSEA analysis revealed that the inflammatory phase was enriched in inflammatory pathways, while the resolution phase comprised pathways related to metabolism and gene rearrangement. By comparing gene clusters differentially expressed in monocytes vs. M1 and vs. M2 macrophages extracted from an in-house created meta-database, it was shown that cells in the model resemble M1 during the inflammatory phase and M2 during resolution. The validation of inflammatory and transcriptional factors by qPCR and ELISA confirmed the transcriptomic profiles in the different phases of inflammation. The accurate description of the development of the human inflammatory reaction provided by this in vitro kinetic model can help in identifying regulatory mechanisms in physiological conditions and during pathological derangements.

Evaluation of antiinflammatory activity of methanol extract of &lt;i&gt; Phyllanthus amarus&lt;/i&gt; in experimental animal models

The effects of methanol extract of Phyllanthus amarus on different phases of inflammation were examined. Investigations were performed using different phlogistic agents-induced paw edema, carrageenan-induced air-pouch inflammation and cotton pellet granuloma in rats. Methanol extract of Phyllanthus amarus significantly inhibited carrageenan, bradykinin, serotonin and prostaglandin E1-induced paw edema, but failed to inhibit the histamine-induced paw edema. Maximum inhibition was observed in prostaglandin E1-induced paw edema. In carrageenan air-pouch model, methanol extract of Phyllanthus amarus significantly reduced the volume of exudate and migration of neutrophils and monocytes. The extract significantly decreased formation of granuloma tissue in chronic inflammation model. The present study revealed that methanol extract of Phyllanthus amarus inhibits all the phases of inflammation.

Mechanisms of pain in arthritis

During inflammation in a joint, patients experience hyperalgesia and sometimes resting pain. Hyperalgesia includes stronger pain upon noxious stimulation (e.g. strong pressure or twisting the joint) and the experience of pain when stimuli are applied that are not felt painful under normal conditions (palpation, movements in the working range). Resting pain is felt without intentional stimulation. Neuronal mechanisms involved in arthritic pain are the peripheral sensitization (sensitization of primary afferent fibres supplying the joint) and central sensitization (sensitization of spinal cord neurons). The peripheral sensitization includes the sensitization of so-called polymodal nociceptors (high threshold receptors that are excited under normal conditions by noxious mechanical stimuli) and of silent nociceptors (neurons that are not excited even by noxious mechanical stimuli). When these nociceptors are sensitized in the process of inflammation they are rendered more excitable and then they even respond to normally non-painful stimuli. In addition, the enhanced input from sensitized nociceptors induces hyperexcitability of second-order neurons in the spinal cord. This central sensitization is an increased gain in the spinal nociceptive processing, and sensitized spinal cord neurons show stronger responses to stimulation of inflamed tissue but also to stimulation of adjacent and even remote healthy tissue. Thus the whole pain pathway is sensitized and this explains why, in the inflamed tissue, pain is evoked by stimuli that do not elicit pain under normal conditions [1]. Numerous mediators and ion channels are involved in the activation and sensitization of nociceptive neurons [1]. Importantly, some mediators that are involved in the pathophysiology of inflammation are also involved in the generation of peripheral and central sensitization (e.g. prostaglandins). Cyclooxygenases and prostaglandins in the periphery and in the spinal cord have been important topics in pain research [2]. During development of an acute inflammation in the knee joint, prostaglandin E2 release in the spinal cord is significantly enhanced. This is in part due to an upregulation of cyclooxygenase-2 in the spinal cord that is already seen within 3 hours of inflammation [3]. The application of prostaglandin E2 to the spinal cord produces hyperexcitability of spinal cord neurons similar to peripheral inflammation. When indomethacin is applied to the spinal cord before and during the development of joint inflammation, the development of central sensitization is significantly attenuated [4]. These findings show the importance of spinal prostaglandins in the generation of inflammation-evoked spinal hyperexcitability. However, the spinal administration of indomethacin to the spinal cord after establishment of inflammation did not reduce responses of spinal cord neurons to mechanical stimulation of the inflamed joint, raising the question of how important spinal prostaglandins are in the maintenance of spinal hyperexcitability [4]. Prostaglandin E2 acts through EP1, EP2, EP3 and EP4 receptors. The generation of spinal hyperexcitability by spinal prostaglandin E2 can be mimicked by spinal application of agonists at the EP1, EP2 and EP4 receptors. When the joint is inflamed and hyperexcitability is established, EP2 and EP4 receptor agonists fail to change responses of spinal cord neurons to mechanical stimulation of the joint. Interestingly, however, the spinal application of an agonist at the EP3 alpha receptor even reduced responses although it had no effect under normal conditions [5]. Thus considerable plasticity of EP receptor activation seems to determine the precise role of spinal prostaglandins in different phases of inflammation.

Anti-inflammatory activity of Syzygium cumini bark

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.

The Role of Nitric Oxide in Inflammation

Publisher Summary This chapter examines the multiple roles that nitric oxide (NO) may play during the inflammatory response. The majority of data implicating a role for NO in inflammation is based on experiments using nitric oxide synthase inhibitors. Inflammation results from increases in vascular flow, alterations in endothelium that can lead to plasma protein and leukocyte extravasation, and finally, the emigration of leukocytes from the circulation to the site of injury with resultant activation of effector cell mechanisms. There is evidence that NO can play a role during each stage of inflammation; the chapter discusses NO in the context of each of these stages. Conflicting data exist in the literature regarding the role of NO during inflammation. Some conflicts arise because of differences in the experimental systems studied such as in the animal species used or in the type of inflammatory stimulus. However, other differences may represent distinct physiologic and pathologic effects of NO during different phases of inflammation. NO plays a multifaceted role in all phases of the inflammatory immune response depending on the source and quantity of NO produced. It is important in the development of therapeutic modalities based on NO biochemistry and biology to take all roles of NO into consideration when designing potential treatments.