Chronification Of Inflammation Research Articles

A Synthetic View on Acanthamoeba Keratitis Host Immune Response: Potential Factors Influencing the Development of Chronic Inflammation

Purpose: The purpose of this study was to compile the current knowledge concerning Acanthamoeba keratitis (AK) host immune response to better understand the elements involved in the chronification of inflammation and worse disease outcomes. Methods: A scoping review of the literature on AK host immune response was written after a systematic literature search was performed on the PubMed, Latin American Caribbean Health Sciences Literature, Cochrane Library, Embase, Web of Science, and Scientific Electronic Library Online databases. Recovered articles were screened according to inclusion and exclusion criteria, and the selected studies were analyzed to compile the review. Results: The search strategy yielded a total of 768 articles from all searched databases. After the exclusion of duplicate records, 412 studies were screened according to inclusion and exclusion criteria. Finally, a total of 95 articles were selected to compile this review, of which 15 were included as additional bibliography. As for study type, 45 were experimental, 19 were observational, 23 were case reports, and 8 were reviews. Conclusions: From the literature, both innate and adaptive immune systems seem to play an important role in AK control and resolution. On the other hand, there is also abundant evidence pointing out that the development of chronic and extracorneal inflammation is immune mediated and is influenced by several factors such as individual patient genetic variability, inadequate treatment, and Acanthamoeba strain pathogenicity.

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

Differential Expression of Inflammarafts in Macrophage Foam Cells and in Nonfoamy Macrophages in Atherosclerotic Lesions-Brief Report.

Reprogramming of monocytes and macrophage manifests in hyperinflammatory responses and chronification of inflammation in atherosclerosis. Recent studies focused on epigenetic, transcriptional, and metabolic alterations that characterize trained immunity. However, the underlying effector mechanisms driving the hyperinflammatory response of reprogrammed macrophages remain unclear. We hypothesized that the plasma membrane of atherosclerotic lesion macrophages undergoes reprogramming to maintain inflammarafts, enlarged lipid rafts (LR) serving as a platform for assembly of inflammatory receptor complexes. Single-cell suspensions from the aortae of Western diet-fed Ldlr-/- mice were gated for BODIPY-high foamy and BODIPY-low nonfoamy F4/80 macrophages by flow cytometry. Inflammarafts were characterized by increased levels of LR, TLR4 (toll-like receptor-4) localization to LR, TLR4 dimers, and the proximity between TLR2, TLR1, and CD36. In a cellular model of trained immunity, LR, TLR4 dimers, and the inflammatory response were measured in bone marrow-derived macrophages subjected to a 24-hour treatment with LPS (lipopolysaccharide) or OxLDL (oxidized low-density lipoprotein), followed by a 6-day wash-out period. Nonfoamy macrophages, which constituted ≈40% of macrophages in atherosclerotic lesions, expressed significantly higher levels of LR and TLR4 dimers, as well as proximity ligation signals for TLR4-LR, TLR2-CD36, and TLR2-TLR1 complexes, compared with foamy macrophages. These inflammaraft measures associated, to a different degree, with plasma cholesterol and inflammatory cytokines, as well as the size of the atherosclerotic lesions and necrotic cores. The bone marrow-derived macrophages trained with LPS simulated nonfoamy atherosclerotic lesion macrophages and continued to express inflammarafts and inflammatory genes for 6 days after LPS removal and displayed a hyperinflammatory response to Pam3CSK4, a TLR2/TLR1 agonist. OxLDL-exposed, lipid-laden macrophages did not express inflammarafts. Our data support the hypothesis that persistent inflammarafts in nonfoamy macrophages in atherosclerotic lesions serve as effectors of macrophage reprogramming into a hyperinflammatory phenotype.

Sore throat in children: diagnosis, treatment, prevention

Introduction. Sore throat often accompanies acute pharyngitis and tonsillitis in both children and adults. Inflammation of the posterior pharyngeal wall, acute pharyngitis, almost never occurs in isolated form in children and is often accompanied by symptoms of acute adenoiditis and / or tonsillitis.Aim. To study the effectiveness of the treatment of exacerbation of chronic non-streptococcal tonsillitis with an antiseptic herbal product in childhood.Materials and methods. We examined 58 children diagnosed with exacerbation of chronic tonsillitis for the period from June 2018 to December 2019. The age of the children ranged from 6 years 4 months up to 14 years old, the average age was 8.3 + 2.4 years, the group included 32 boys (55%) and 26 girls (45%). The duration of the disease ranged from 1 to 5.5 years. The exacerbations of chronic tonsillitis occured 3-4 times a year. The patients included in the study received the antiseptic herbal product in the form of drops at a dose of 15 drops five times/day for 7 days, and then 15 drops three times/day for another 7 days. The course of therapy was 14 days.Results. The provided course of therapy resulted in the significant positive changes overtime: reduced intensity of complaints already at the second visit, significant reduction of complaints at the third visit and actual relief of complaints by the fourth visit in the patients receiving the monotherapy with antiseptic herbal product.Conclusions. Preservation of the normal microbiome of the upper respiratory tract in children maintains effective functioning of MALT and thereby reduces the risk of the development and chronification of inflammation in the oropharynx. The antiseptic herbal medicinal product may be regarded as the alternative to antibiotic therapy in children with exacerbation of chronic tonsillitis, as it has a multifunctional effect on the mucous membranes lining upper respiratory tract, stimulates innate and adaptive immunity, and increases the resistance of mucous membranes to the pathogens.

Do Mitochondrial DNA Mutations Play a Key Role in the Chronification of Sterile Inflammation? Special Focus on Atherosclerosis.

The aim of the elucidation of mechanisms implicated in the chronification of inflammation is to shed light on the pathogenesis of disorders that are responsible for the majority of the incidences of diseases and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally. Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity. In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions. A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in response to the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response, resulting in the chronification of inflammation in atherosclerosis.

Cellular Mechanisms of Human Atherogenesis: Focus on Chronification of Inflammation and Mitochondrial Mutations.

Atherosclerosis is one of the most common diseases of the cardiovascular system that leads to the development of life-threatening conditions, such as heart attack and stroke. Arthrosclerosis affects various arteries in the human body, but is especially dangerous in the arteries alimenting heart and brain, aorta, and arteries of the lower limbs. By its pathophysiology, atherosclerosis is an inflammatory disease. During the pathological process, lesions of arterial intima in the form of focal thickening are observed, which form atherosclerotic plaques as the disease progresses further. Given the significance of atherosclerosis for the global health, the search for novel effective therapies is highly prioritized. However, despite the constant progress, our understanding of the mechanisms of atherogenesis is still incomplete. One of the remaining puzzles in atherosclerosis development is the focal distribution of atherosclerotic lesions in the arterial wall. It implies the existence of certain mosaicism within the tissue, with some areas more susceptible to disease development than others, which may prove to be important for novel therapy development. There are many hypotheses explaining this phenomenon, for example, the influence of viruses, and the spread in the endothelium of the vessel multinucleated giant endothelial cells. We suggest the local variations of the mitochondrial genome as a possible explanation of this mosaicism. In this review, we discuss the role of genetic variations in the nuclear and mitochondrial genomes that influence the development of atherosclerosis. Changes in the mitochondrial and nuclear genome have been identified as independent factors for the development of the disease, as well as potential diagnostic markers.

Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis.

Chronification of inflammation is the process that lies at the basis of several human diseases that make up to 80% of morbidity and mortality worldwide. It can also explain a great deal of processes related to aging. Atherosclerosis is an example of the most important chronic inflammatory pathology in terms of public health impact. Atherogenesis is based on the inflammatory response of the innate immunity arising locally or focally. The main trigger for this response appears to be modified low-density lipoprotein (LDL), although other factors may also play a role. With the quick resolution of inflammation, atherosclerotic changes in the arterial wall do not occur. However, a violation of the innate immunity response can lead to chronification of local inflammation and, as a result, to atherosclerotic lesion formation. In this review, we discuss possible mechanisms of the impaired immune response with a special focus on mitochondrial dysfunction. Some mitochondrial dysfunctions may be due to mutations in mitochondrial DNA. Several mitochondrial DNA mutations leading to defective mitophagy have been identified. The regulatory role of mitophagy in the immune response has been shown in recent studies. We suggest that defective mitophagy promoted by mutations in mitochondrial DNA can cause innate immunity disorders leading to chronification of inflammation.

Expression of extracellular RNA in synovial tissue and RNase activity in synovial fluid of rheumatoid arthritis patients

BackgroundRNA is required for protein biosynthesis. However, extracellular RNA (exRNA) is also present within tissues and actively secreted by cells. Examples for the exRNA-activity are a pro-coagulative effect and an...

Inflammation in Parkinson's disease: the role of activated microglia

Glial inflammation was viewed previously as a bystander effect, or epiphenomenon, with inflammation occurring when damaged neurons elicit an activation response by glia. However, an accumulating body of evidence has challenged this perspective and indicates an active role of neuroinflammation in the pathophysiology of neurodegenerative disorders as Parkinson's disease (PD). Agents suppressing microglial activation are attracting attention as candidate drugs for neuroprotection in PD: While different mechanisms including environmental toxins and genetic factors initiate neuronal damage in the basal ganglia in PD, there is now unequivocal evidence that activation of neuroinflammatory cells, especially microglia aggravates this neurodegenerative process. It was shown that following an acute exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) the degenerative process continues for years in absence of the toxin. Large numbers of reactive microglia have been observed in the substantia nigra of PD patients, indicating that this inflammatory process aggravates neurodegeneration. By releasing various kinds of noxious factors such as cytokines or proinflammatory molecules microglia may damage CNS cells. The stimuli triggering microgliosis in Parkinsonian syndromes are unknown: However, analysis of neuronal loss in PD patients shows that it is not uniform but that neurons containing neuromelanin (NM) are predominantly involved. We hypothesized that extraneuronal melanin might trigger microgliosis, chemotaxis and microglial activation in PD with subsequent release of proinflammatory and possible neurotoxic mediators like NO, TNF-alpha and IL-6. The addition of human NM to microglial cell cultures induced positive chemotactic effects, and led to an upregulation of TNF-alpha, IL-6 and NO. To further investigate the possible role of NM in the pathogenesis of PD we conducted in vivo experiments which showed that microglial cells become activated and neurotoxic after injection of human neuromelanin (NM) into the substantia nigra as compared to control animals injected with gold particles of comparable size and weight. These findings demonstrate a crucial role of NM in the pathogenesis of Parkinson's disease by augmentation of microglial activation, leading to a vicious cycle of neuronal death, exposure of additional neuromelanin and chronification of inflammation.

Inflammation in Parkinsons Diseases and Other Neurodegenerative Diseases: Cause and Therapeutic Implications

Agents suppressing microglial activation are attracting attention as candidate drugs for neuroprotection in Parkinson s disease (PD): While different mechanisms including environmental toxins and genetic factors initiate neuronal damage in the substantia nigra and striatum in PD, there is unequivocal evidence that activation of neuroinflammatory cells aggravates this neurodegenerative process. It was shown that following an acute exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and other toxins the degenerative process continues for years in absence of the toxin. Reactive microglia has been observed in the substantia nigra of patients with PD, indicating that this inflammatory process might aggravate neurodegeneration. By releasing various kinds of noxious factors such as cytokines or proinflammatory molecules microglia may damage CNS cells. The stimuli triggering microgliosis in Parkinsonian syndromes are unknown so far: However, analysis of neuronal loss in PD patients shows that it is not uniform but that neurons containing neuromelanin (NM) are predominantly involved. We hypothesized that extraneuronal melanin might trigger microgliosis, microglial chemotaxis and microglial activation in PD with subsequent release of neurotoxic mediators. The addition of human NM to microglial cell cultures induced positive chemotactic effects, activated the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB) via phosphorylation and degradation of the inhibitor protein kappaB (IkappaB), and led to an upregulation of TNF-alpha, IL-6 and NO. These findings demonstrate a crucial role of NM in the pathogenesis of Parkinson's disease by augmentation of microglial activation, leading to a vicious cycle of neuronal death, exposure of additional neuromelanin and chronification of inflammation. Antiinflammatory drugs may be one of the new approaches in the treatment of PD.

Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease.

It has been suggested that microglial inflammation augments the progression of Parkinson's disease (PD). However, endogenous factors initiating microglial activation are largely unknown. We therefore investigated the effects of human neuromelanin (NM) on the release of neurotoxic mediators and the underlying signaling pathways from rat microglia in vitro. The addition of NM to microglial cultures induced positive chemotactic effects, activated the proinflammatory transcription factor nuclear factor kappaB (NF-kappaB) via phosphorylation and degradation of the inhibitor protein kappaB (IkappaB), and led to an up-regulation of tumor necrosis factor alpha, interleukin-6, and nitric oxide. The impairment of NF-kappaB function by the IkappaB kinase inhibitor sulfasalazine was paralleled by a decline in neurotoxic mediators. NM also activated p38 mitogen-activated protein kinase (MAPK), the inhibition of this pathway by SB203580 diminished phosphorylation of the transactivation domain of the p65 subunit of NF-kappaB. These findings demonstrate a crucial role of NM in the pathogenesis of PD by augmentation of microglial activation, leading to a vicious cycle of neuronal death, exposure of additional neuromelanin, and chronification of inflammation. The antagonization of microglial activation by a pharmacological intervention targeting microglial NF-kappaB or p38 MAPK could point to additional venues in the treatment of PD.