HMGB-1 in Psoriasis

Psoriasis is a multifactorial pathology linked to systemic inflammation. Enhanced keratinocytes proliferation and a minor maturation state of the cells are typical features. Perivascular T cells, dendritic cells, macrophages, and neutrophilic granulocytes are part of the scenario completed by apoptosis dysregulation. Several proinflammatory mediators, alarmins and growth factors are increased too, both in the skin and the patients’ blood. HMGB1 is important as an alarmin in several inflammatory conditions. Released after cellular damage, HMGB1 acts as a danger signal. Several studies have considered its role in psoriasis pathogenesis. We evaluated its level in psoriasis and the potential of the alarmin blockade through standard therapies, biological treatments and using monoclonal antibodies. PV patients were shown to have significantly increased levels of HMGB1 both in lesional skin and in serum, which were linked, in some cases, to other pro-inflammatory markers and alarmins. In most cases these parameters were correlated with PASI score. Data demonstrated that blocking HMGB1 is effective in ameliorating psoriasis. Focusing on this approach could be valuable in terms of a therapeutic option for counteracting immune-related diseases in a way unthinkable until few years ago.

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Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature

Frontiers in Medicine ◽

10.3389/fmed.2021.661101 ◽

2021 ◽

Vol 8 ◽

Author(s):

Per Eriksson ◽

Johan Mölne ◽

Lina Wirestam ◽

Christopher Sjöwall

Keyword(s):

Ankylosing Spondylitis ◽

Therapeutic Option ◽

Relevant Literature ◽

Acute Phase Reactant ◽

Renal Amyloidosis ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Beneficial Effects ◽

Amyloid A ◽

Inflammatory Conditions

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

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Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

BioMed Research International ◽

10.1155/2020/1605358 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Wellington Caio-Silva ◽

Danielle da Silva Dias ◽

Carolina Victoria Cruz Junho ◽

Karine Panico ◽

Raquel Silva Neres-Santos ◽

...

Keyword(s):

Nitric Oxide ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Cardiorenal Syndrome ◽

Redox Balance ◽

Renal Ischemia ◽

Cellular Damage ◽

Cellular Mechanisms ◽

Inflammatory Conditions

In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.

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Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

Autoimmune Diseases ◽

10.1155/2012/346501 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Claudio Blasi ◽

Eunjung Kim ◽

Anne A. Knowlton

Keyword(s):

Metabolic Syndrome ◽

Inflammatory Markers ◽

Diabetic Control ◽

Intensive Treatment ◽

Blood Levels ◽

Ros Production ◽

Proinflammatory Mediators ◽

Before And After ◽

Antibody Titers ◽

Antibody Levels

The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP)60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001) and BMI (P<0.001). After treatment, there was a significant decrease in IL-6 (P<0.05). HSP60 levels were before treatment−6.9+1.9, after treatment−7.1+2.0 ng/mL (P=ns). Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

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Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-κB

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00388.2006 ◽

2007 ◽

Vol 292 (4) ◽

pp. L960-L971 ◽

Cited By ~ 110

Author(s):

Huili Zhang ◽

Liang Zhi ◽

Shabbir Moochhala ◽

Philip K. Moore ◽

Madhav Bhatia

Keyword(s):

Hydrogen Sulfide ◽

Systemic Inflammation ◽

Lung Inflammation ◽

Cecal Ligation ◽

Cecal Ligation And Puncture ◽

Protein Levels ◽

Proinflammatory Mediators ◽

Inflammatory Conditions ◽

Cytokines And Chemokines ◽

Inflammatory Protein

Recent studies have implied that hydrogen sulfide (H2S) plays a crucial role in several inflammatory conditions. However, so far little is known about the mechanism by which H2S provokes the inflammatory response in sepsis. Thus the aim of this study was to investigate if H2S regulates sepsis-associated systemic inflammation and production of proinflammatory mediators via the activation of NF-κB. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with dl-propargylglycine (PAG; 50 mg/kg ip), NaHS (10 mg/kg ip), or saline. PAG, an inhibitor of H2S formation, was administered either 1 h before or 1 h after CLP, whereas NaHS, an H2S donor, was given at the time of CLP. Some normal mice were given NaHS (10 mg/kg ip) to induce lung inflammation with or without pretreatment with the NF-κB inhibitor BAY 11-7082. Eight hours after CLP, both prophylactic and therapeutic administration of PAG significantly reduced the mRNA and protein levels of IL-1β, IL-6, TNF-α, monocyte chemotactic protein-1, and macrophage inflammatory protein-2 in lung and liver coupled with decreased activation and translocation of NF-κB in lung and liver. Inhibition of H2S formation also significantly reduced lung permeability and plasma alanine aminotransferase activity. In contrast, injection of NaHS significantly aggravated sepsis-associated systemic inflammation and increased NF-κB activation. In addition, H2S-induced lung inflammation was blocked by BAY 11-7082. Therefore, H2S upregulates the production of proinflammatory mediators and exacerbates the systemic inflammation in sepsis through a mechanism involving NF-κB activation.

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P2X7 Receptor Blockade Protects Against Acrolein-Induced Bladder Damage: A Potential New Therapeutic Approach for the Treatment of Bladder Inflammatory Diseases

Frontiers in Pharmacology ◽

10.3389/fphar.2021.682520 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhinoos Taidi ◽

Tommy Zhou ◽

Kate H. Moore ◽

Kylie J. Mansfield ◽

Lu Liu

Keyword(s):

Oxidative Stress ◽

Urinary Bladder ◽

Receptor Antagonist ◽

P2x7 Receptor ◽

Ex Vivo ◽

Therapeutic Option ◽

Bladder Wall ◽

Loss Of Function ◽

Inflammatory Conditions

Inflammatory conditions of the urinary bladder have been shown to be associated with urothelial damage and loss of function. The purinergic P2X7 receptor has been implicated in several inflammatory conditions. The aim of this study was to investigate the role of the P2X7 receptor in acrolein-induced inflammatory damage using the porcine urinary bladder. For this purpose, an ex-vivo model of porcine urothelial damage induced by direct instillation of acrolein into the whole bladder lumen was used. To determine the role of the P2X7 receptor, the bladders were pre-incubated with a selective P2X7 receptor antagonist, A804598 (10 μM), for 1 h. The effects of the acrolein-induced urothelial damage on the bladder’s function were assessed by examining the bladder wall contractile response, structure changes, apoptosis, and oxidative stress in the bladder tissues. The acrolein treatment led to significant damage to the urothelium histology, tight junction expression, and contractile responses. Acrolein also induced apoptosis in the mucosa layer. All these acrolein-induced responses were attenuated by pre-treatment with the P2X7 receptor antagonist A804598. Acrolein also significantly induced DNA oxidation in the submucosal layer; however, the P2X7 receptor antagonism did not show any protective effect towards the acrolein-induced oxidative stress. These findings suggested that the P2X7 receptor is involved in the acrolein-induced damage to the urothelium; therefore, the P2X7 receptor antagonists may be a new therapeutic option for the treatment of bladder inflammation.

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Therapeutic Plasma Exchange Using Convalescent Plasma Replacement Therapy in Severe COVID-19 Infections: A Potential Therapeutic Option

EMJ Innovation ◽

10.33590/emjinnov/20-00183 ◽

2021 ◽

pp. 78-81

Author(s):

Joy Varghese ◽

Pushkala Subramanian ◽

Venkataraman Jayanthi

Keyword(s):

Public Health ◽

Plasma Exchange ◽

Inflammatory Markers ◽

Therapeutic Option ◽

Public Health Emergency ◽

Therapeutic Plasma Exchange ◽

Cytokine Storm ◽

Global Public Health ◽

Plasma Therapy ◽

Key Factor

Currently, the coronavirus disease (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is a major global public health emergency. Cytokine storm is a key factor and plays a major role in disease severity and clinical outcome. Recently, the literature reveals the use of therapeutic plasma exchange to reduce the inflammatory markers. Evidence also exists for the use of convalescent plasma therapy in patients with severe COVID-19. This brief communication explores the advantages on therapeutic plasma exchange with convalescent plasma in patients with moderate-to-severe COVID-19.

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Ultrasound for the treatment of acute kidney injury and other inflammatory conditions: a promising path toward noninvasive neuroimmune regulation

AJP Renal Physiology ◽

10.1152/ajprenal.00145.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. F125-F138

Author(s):

Jieru Cai ◽

William T. Nash ◽

Mark D. Okusa

Keyword(s):

Acute Kidney Injury ◽

Nervous System ◽

Inflammatory Diseases ◽

Therapeutic Option ◽

Kidney Injury ◽

Pulsed Ultrasound ◽

Clinical Disorder ◽

Inflammatory Conditions ◽

High Prevalence ◽

Novel Strategy

Acute kidney injury (AKI) is an important clinical disorder with high prevalence, serious consequences, and limited therapeutic options. Modulation of neuroimmune interaction by nonpharmacological methods is emerging as a novel strategy for treating inflammatory diseases, including AKI. Recently, pulsed ultrasound (US) treatment was shown to protect from AKI by stimulating the cholinergic anti-inflammatory pathway. Because of the relatively simple, portable, and noninvasive nature of US procedures, US stimulation may be a valuable therapeutic option for treating inflammatory conditions. This review discusses potential impacts of US bioeffects on the nervous system and how this may generate feedback onto the immune system. We also discuss recent evidence supporting the use of US as a means to treat AKI and other inflammatory diseases.

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PathogenicMannheimia haemolyticaInvades Differentiated Bovine Airway Epithelial Cells

Infection and Immunity ◽

10.1128/iai.00078-19 ◽

2019 ◽

Vol 87 (6) ◽

Cited By ~ 8

Author(s):

Daniel Cozens ◽

Erin Sutherland ◽

Miquel Lauder ◽

Geraldine Taylor ◽

Catherine C. Berry ◽

...

Keyword(s):

Epithelial Cells ◽

Respiratory Tract ◽

Bacterial Species ◽

Airway Epithelial Cells ◽

Cellular Damage ◽

Economic Losses ◽

Bacterial Invasion ◽

Airway Epithelial ◽

Content Type ◽

Proinflammatory Mediators

ABSTRACTThe Gram-negative bacteriumMannheimia haemolyticais the primary bacterial species associated with bovine respiratory disease (BRD) and is responsible for significant economic losses to livestock industries worldwide. Healthy cattle are frequently colonized by commensal serotype A2 strains, but disease is usually caused by pathogenic strains of serotype A1. For reasons that are poorly understood, a transition occurs within the respiratory tract and a sudden explosive proliferation of serotype A1 bacteria leads to the onset of pneumonic disease. Very little is known about the interactions ofM. haemolyticawith airway epithelial cells of the respiratory mucosa which might explain the different abilities of serotype A1 and A2 strains to cause disease. In the present study, host-pathogen interactions in the bovine respiratory tract were mimicked using a novel differentiated bovine bronchial epithelial cell (BBEC) infection model. In this model, differentiated BBECs were inoculated with serotype A1 or A2 strains ofM. haemolyticaand the course of infection followed over a 5-day period by microscopic assessment and measurement of key proinflammatory mediators. We have demonstrated that serotype A1, but not A2,M. haemolyticainvades differentiated BBECs by transcytosis and subsequently undergoes rapid intracellular replication before spreading to adjacent cells and causing extensive cellular damage. Our findings suggest that the explosive proliferation of serotype A1M. haemolyticathat occurs within the bovine respiratory tract prior to the onset of pneumonic disease is potentially due to bacterial invasion of, and rapid proliferation within, the mucosal epithelium. The discovery of this previously unrecognized mechanism of pathogenesis is important because it will allow the serotype A1-specific virulence determinants responsible for invasion to be identified and thereby provide opportunities for the development of new strategies for combatting BRD aimed at preventing early colonization and infection of the bovine respiratory tract.

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NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis

International Journal of Molecular Sciences ◽

10.3390/ijms20010057 ◽

2018 ◽

Vol 20 (1) ◽

pp. 57 ◽

Cited By ~ 11

Author(s):

Nicole Ranson ◽

Mark Veldhuis ◽

Brent Mitchell ◽

Scott Fanning ◽

Anthony Cook ◽

...

Keyword(s):

Ulcerative Colitis ◽

Epithelial Cell ◽

Lamina Propria ◽

Immune Cells ◽

Cell Layer ◽

Therapeutic Option ◽

Spatial Relationship ◽

Inflammatory Conditions ◽

Epithelial Cell Layer ◽

Active Disease

A contributing factor in the development of ulcerative colitis (UC) and Crohn’s disease (CD) is the disruption of innate and adaptive signaling pathways due to aberrant cytokine production. The cytokine, interleukin (IL)-1β, is highly inflammatory and its production is tightly regulated through transcriptional control and both inflammasome-dependent and inflammasome- independent proteolytic cleavage. In this study, qRT-PCR, immunohistochemistry, immunofluorescence confocal microscopy were used to (1) assess the mRNA expression of NLRP3, IL-1β, CASP1 and ASC in paired biopsies from UC and CD patient, and (2) the colonic localization and spatial relationship of NLRP3 and IL-1β in active and quiescent disease. NLRP3 and IL-1β were found to be upregulated in active UC and CD. During active disease, IL-1β was localized to the infiltrate of lamina propria immune cells, which contrasts with the near-exclusive epithelial cell layer expression during non-inflammatory conditions. In active disease, NLRP3 was consistently expressed within the neutrophils and other immune cells of the lamina propria and absent from the epithelial cell layer. The disparity in spatial localization of IL-1β and NLRP3, observed only in active UC, which is characterized by a neutrophil-dominated lamina propria cell population, implies inflammasome-independent processing of IL-1β. Consistent with other acute inflammatory conditions, these results suggest that blocking both caspase-1 and neutrophil-derived serine proteases may provide an additional therapeutic option for treating active UC.

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Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Physiological Reviews ◽

10.1152/physrev.00027.2013 ◽

2014 ◽

Vol 94 (3) ◽

pp. 795-858 ◽

Cited By ~ 89

Author(s):

Jaap G. Neels ◽

Paul A. Grimaldi

Keyword(s):

Therapeutic Option ◽

Cell Types ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

In Vivo Models ◽

Physiological Functions ◽

Regulatory Pathways ◽

Inflammatory Conditions

The peroxisome proliferator-activated receptors, PPARα, PPARβ, and PPARγ, are a family of transcription factors activated by a diversity of molecules including fatty acids and fatty acid metabolites. PPARs regulate the transcription of a large variety of genes implicated in metabolism, inflammation, proliferation, and differentiation in different cell types. These transcriptional regulations involve both direct transactivation and interaction with other transcriptional regulatory pathways. The functions of PPARα and PPARγ have been extensively documented mainly because these isoforms are activated by molecules clinically used as hypolipidemic and antidiabetic compounds. The physiological functions of PPARβ remained for a while less investigated, but the finding that specific synthetic agonists exert beneficial actions in obese subjects uplifted the studies aimed to elucidate the roles of this PPAR isoform. Intensive work based on pharmacological and genetic approaches and on the use of both in vitro and in vivo models has considerably improved our knowledge on the physiological roles of PPARβ in various cell types. This review will summarize the accumulated evidence for the implication of PPARβ in the regulation of development, metabolism, and inflammation in several tissues, including skeletal muscle, heart, skin, and intestine. Some of these findings indicate that pharmacological activation of PPARβ could be envisioned as a therapeutic option for the correction of metabolic disorders and a variety of inflammatory conditions. However, other experimental data suggesting that activation of PPARβ could result in serious adverse effects, such as carcinogenesis and psoriasis, raise concerns about the clinical use of potent PPARβ agonists.

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