scholarly journals Immunocompatibility of Rad-PC-Rad liposomes in vitro, based on human complement activation and cytokine release

2018 ◽  
Vol 1 (1) ◽  
pp. 43-62 ◽  
Author(s):  
Sofiya Matviykiv ◽  
Marzia Buscema ◽  
Gabriela Gerganova ◽  
Tamás Mészáros ◽  
Gergely Tibor Kozma ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Alternative Pathway ◽  
White Blood Cells ◽  
Membrane Attack Complex ◽  
Negative Control ◽  
Pro Inflammatory Cytokines

Liposomal drug delivery systems can protect pharmaceutical substances and control their release. Systemic administration of liposomes, however, often activate the innate immune system, resulting in hypersensitivity reactions. These pseudo-allergic reactions can be interpreted as activating the complement system. Complement activation destroys and eliminates foreign substances, either directly through opsonization and the formation of the membrane attack complex (MAC), or by activating leukocytes and initiating inflammatory responses via mediators, such as cytokines. In this study, we investigated the in vitro immune toxicity of the recently synthesized Rad-PC-Rad liposomes, analyzing the liposome-induced complement activation. In five human sera, Rad-PC-Rad liposomes did not induce activation, but in one serum high sensitivity via alternative pathway was detected. Such a behavior in adverse phenomena is characteristic for patient-to-patient variation and, thus, the number of donors should be in the order of hundreds rather than tens, hence the present study based on six donors is preliminary. In order to further prove the suitability of mechano-responsive Rad-PC-Rad liposomes for clinical trials, the production of pro-inflammatory cytokines was examined by human white blood cells. The concentrations of the pro-inflammatory cytokines, IL-6, IL-12p70, TNF-α, and IL-1β, induced by Rad-PC-Rad liposomal formulations, incubated with whole blood samples, were smaller or comparable to saline (negative control). Because of this favorable in vitro hemo-compatibility, in vivo investigations using these mechano-responsive liposomes should be designed.

scholarly journals Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

2021 ◽  
Author(s):  
Cheng Ding ◽  
Chuang Yang ◽  
Tao Cheng ◽  
Xingyan Wang ◽  
Qiaojie Wang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Total Joint Replacement ◽  
Major Complication ◽  
Dual Model ◽  
Joint Replacement Surgery ◽  
Pro Inflammatory Cytokines ◽  
Macrophage Membrane

Abstract Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

MiR-195-5p inhibits the development of chronic obstructive pulmonary disease via targeting siglec1

2020 ◽  
Vol 39 (10) ◽  
pp. 1333-1344
Author(s):  
S Li ◽  
L Jiang ◽  
Y Yang ◽  
J Cao ◽  
Q Zhang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Pulmonary Macrophages ◽  
Pro Inflammatory Cytokines

Chronic obstructive pulmonary disease (COPD), characterized by chronic inflammation, is a recognized global health crisis. Sialic acid-binding immunoglobulin-like lectin 1 (siglec1 or CD169), mainly expressed in macrophages and dendritic cells, is markedly upregulated after encountering pathogens or under acute/chronic inflammation conditions. However, it is rarely reported that whether siglec1 plays a role in the development of COPD. In this study, we found that siglec1 had higher expression in the lungs from COPD rats and in peripheral blood mononuclear cells (PBMCs) from COPD patients. Knockdown of siglec1 in vivo and in vitro dramatically decreased pro-inflammatory cytokines production in pulmonary macrophages and alleviated pulmonary inflammatory responses in COPD rats as well as inactivated nuclear factor kappa B (NF-κB) signaling. In addition, we identified a new microRNA, miR-195-5p, which has never explored in COPD, was lower expressed in COPD rats and PBMC of COPD patients, and could negatively modulate siglec1 expression in macrophages. Moreover, overexpression of miR-195-5p via miR-195-5p mimics in vitro and in vivo could significantly alleviate pro-inflammatory cytokines production in pulmonary macrophages and pulmonary inflammatory responses in COPD rats. Together, our findings suggested that miR-195-5p inhibited the development of COPD via targeting siglec1, which might become a therapeutic target to improve COPD.

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

2020 ◽  
Vol 35 (3) ◽  
pp. 233-238
Author(s):  
Muflihatul Muniroh
Keyword(s):  
Inflammatory Cytokines ◽  
Health Concern ◽  
Brain Cells ◽  
Preventive Strategy ◽  
Hearing Impairments ◽  
Sensory Disturbances ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

scholarly journals Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

2020 ◽  
Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Nk Cell ◽  
Inflammatory Monocytes ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

scholarly journals Pro-Inflammatory Cytokines Reduce the Proliferation of NG2 Cells and Increase Shedding of NG2 In Vivo and In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109387 ◽  
Author(s):  
Malin Wennström ◽  
Shorena Janelidze ◽  
Cecilie Bay-Richter ◽  
Lennart Minthon ◽  
Lena Brundin
Keyword(s):  
Inflammatory Cytokines ◽  
Ng2 Cells ◽  
Pro Inflammatory Cytokines

scholarly journals Steroid Sulfates from Ophiuroids (Brittle Stars): Action on Some Factors of Innate and Adaptive Immunity

2016 ◽  
Vol 11 (6) ◽  
pp. 1934578X1601100
Author(s):  
Anna K Gazha ◽  
Lyudmila A. Ivanushko ◽  
Eleonora V. Levina ◽  
Sergey N. Fedorov ◽  
Tatyana S. Zaporozets ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Cytokines ◽  
Brittle Stars ◽  
Innate And Adaptive Immunity ◽  
Functional Activities ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The action of seven polyhydroxylated sterol mono- and disulfates (1-7), isolated from ophiuroids, on innate and adaptive immunity was examined in in vitro and in vivo experiments. At least, three of them (1, 2 and 4) increased the functional activities of neutrophils, including levels of oxygen-dependent metabolism, adhesive and phagocytic properties, and induced the expression of pro-inflammatory cytokines TNF-α and IL-8. Compound 4 was the most active for enhancing the production of antibody forming cells in the mouse spleen.

scholarly journals A stealth adhesion factor contributes toVibrio vulnificuspathogenicity: Flp pili play roles in host invasion, survival in the blood stream and resistance to complement activation

2019 ◽  
Author(s):  
Tra–My Duong–Nu ◽  
Kwangjoon Jeong ◽  
Soo Young Kim ◽  
Wenzhi Tan ◽  
Sao Puth ◽  
...  
Keyword(s):  
Host Cell ◽  
Complement Activation ◽  
Vibrio Vulnificus ◽  
Alternative Pathway ◽  
Molecular Genetic ◽  
Wild Type ◽  
Triple Mutant ◽  
Mutant Cells

AbstractThe tad operons encode the machinery required for adhesive Flp (fimbrial low-molecular-weight protein) pili biogenesis.Vibrio vulnificus, an opportunistic pathogen, harbors three distincttadloci. Among them, onlytad1locus was highly upregulated inin vivogrowing bacteria compared toin vitroculture condition. To understand the pathogenic roles of the threetadloci during infection, we constructed single, double and triple tad loci deletion mutants. Interestingly, only theΔtad123triple mutant cells exhibited significantly decreased lethality in mice. Ultrastructural observations revealed short, thin filamentous projections disappeared on theΔtad123mutant cells. Since the pilin was paradoxically non-immunogenic, a V5 tag was fused to Flp to visualize the pilin protein by using immunogold EM and immunofluorescence microscopy. TheΔtad123mutant cells showed attenuated host cell adhesion, delayed RtxA1 exotoxin secretion and subsequently impaired translocation across the intestinal epithelium compared to wild type, which could be partially complemented with each wild type operon. TheΔtad123mutant was susceptible to complement-mediated bacteriolysis, predominantly via the alternative pathway, suggesting stealth hiding role of the Tad pili. Taken together, all threetadloci cooperate to confer successful invasion ofV. vulnificusinto deeper tissue and evasion from host defense mechanisms, ultimately resulting in septicemia.Author SummaryTo understand the roles of the three Tad operons in the pathogenesis ofV. vulnificusinfection, we constructed mutant strain with single, double and triple Tad loci deletions. Employing a variety of mouse infection models coupled with molecular genetic analyses, we demonstrate here that all three Tad operons are required forV. vulnificuspathogenicity as the cryptic pili contribute to host cell and tissue invasion, survival in the blood, and resistance to complement activation.

scholarly journals MicroRNA-155 Expression Is Associated With Pulpitis Progression By Targeting SHIP1

2021 ◽  
Author(s):  
Baishun Li ◽  
Liyang Guo ◽  
Ying He ◽  
Xinran Tu ◽  
Jialin Zhong ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protein Level ◽  
Bioinformatics Analysis ◽  
Inflammatory Responses ◽  
Akt Signaling Pathway ◽  
Oral Inflammation ◽  
Direct Target ◽  
Pro Inflammatory Cytokines

Abstract Pulpitis is a commonly seen oral inflammation condition in clinical practice, it can cause much pain for the patient and may induce infections in other systems. Much is still unknown for the pathogenic mechanism of pulpitis. In this work, we discovered that the expression of miR-155 was associated with dental pulpal inflammation both in vivo and in vitro. Experiments on odontoblast cell line MDPC-23 showed miR-155 could act as a positive regulator by increasing the production of pro-inflammatory cytokines IL-1β and IL-6 during inflammatory responses, whereas knockdown of miR-155 can reverse the effects. Bioinformatics analysis demonstrated that SHIP1 is a direct target of miR-155 in odontoblasts, this result was further verified at both mRNA and protein level. Inhibition of miR-155 resulted in the downregulation of inflammation factors, while co-transfection of si-SHIP1 and miR-155 inhibitor promoted the inflammatory responses. Treatment with miR-155 mimic or si-SHIP1 up-regulated the protein level of p-PI3K and p-AKT. By contrast, miR-155 inhibitor exerted the opposite effects. miR-155 mimics could upregulated the gene expression of IL-1β and IL-6. Co-transfection of LY294002 and miR-155 mimic attenuated the inflammatory responses. Consistent with in vitro results, miR-155-/- mice could alleviate inflammatory response, as well as decrease the activation of p-PI3K and p-AKT, whereas increase the activation of SHIP1. In conclusion, these data revealed a novel role for miR-155 in regulation of dental pulpal inflammatory response by targeting SHIP1 through PI3K/AKT signaling pathway.

scholarly journals The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Leon Islas-Weinstein ◽  
Brenda Marquina-Castillo ◽  
Dulce Mata-Espinosa ◽  
Iris S. Paredes-González ◽  
Jaime Chávez ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Cholinergic System ◽  
Respiratory Infections ◽  
Lung Epithelial Cells ◽  
Cellular Expression ◽  
Α7 Nachr ◽  
Pro Inflammatory Cytokines

The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.

scholarly journals ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
W. Posch ◽  
J. Vosper ◽  
V. Zaderer ◽  
A. Noureen ◽  
S. Constant ◽  
...  
Keyword(s):  
Medical Device ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Productive Infection ◽  
Tissue Destruction ◽  
Virus Binding ◽  
Epithelial Integrity ◽  
Human Airway

ABSTRACT SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium. IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.

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