Glycoinositolphospholipids from Trypanosoma cruzi Interfere with Macrophages and Dendritic Cell Responses

ABSTRACT To investigate the possible effects of glycoinositolphospholipid (GIPL) from Trypanosoma cruzi on human antigen presenting cells, we tested their effects on lipopolysaccharide (LPS)-stimulated human macrophages and dendritic cells (DC). Human macrophages or DC were incubated with GIPL (50 μg/ml) and LPS (500 pg/ml) and tumor necrosis factor alpha (TNF-α), interleukin 8 (IL-8), IL-10, and IL-12p40 levels in supernatants were analyzed by enzyme-linked immunosorbent assay. TNF-α, IL-10, and IL-12 secretion were significantly decreased by GIPL both in macrophages and DC. In contrast, GIPL did not alter IL-8 production. We also analyzed the expression of CD80, CD86, HLA-DR, CD40, and CD57 on the macrophage surface after stimulation with LPS in the presence or absence of T. cruzi GIPL. GIPL led to a down-regulation in the expression of all tested molecules. We additionally examined the influence of T. cruzi GIPL on the response of human DC to LPS. LPS-induced HLA-DR, CD83, and CD86 up-regulation was significantly inhibited by GIPL. A slight down-regulation in CD80 and CD40 expression on DC surfaces in the presence of GIPL was also noticed. Similarly, GIPL led to down-modulation of CD83, CD80, CD86, and HLA-DR surface expression and TNF-α and IL-10 production when DC were stimulated by CD40L. The ceramide portion of GIPL was responsible for most of the activity exhibited by the whole molecule. Considering the important role of the immune response in determining the fate of the host-parasite relationship, the immunoregulatory activities of T. cruzi GIPL are potentially important for parasite evasion and then pathogenesis of infection with protozoan parasites.

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Abundant Secretion of Bioactive Interleukin-1β by Human Macrophages Induced by Actinobacillus actinomycetemcomitans Leukotoxin

Infection and Immunity ◽

10.1128/iai.73.1.453-458.2005 ◽

2005 ◽

Vol 73 (1) ◽

pp. 453-458 ◽

Cited By ~ 51

Author(s):

P. Kelk ◽

R. Claesson ◽

L. Hänström ◽

U. H. Lerner ◽

S. Kalfas ◽

...

Keyword(s):

Actinobacillus Actinomycetemcomitans ◽

Interleukin 1Β ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Human Macrophages ◽

Specific Antibodies ◽

Protein Levels ◽

Caspase 1 ◽

Reverse Transcription Pcr ◽

Tnf Α

ABSTRACT Actinobacillus actinomycetemcomitans produces a leukotoxin that selectively kills human leukocytes. Recently, we reported that macrophages are highly sensitive to leukotoxin and that their lysis involves activation of caspase 1. In this study, we show that leukotoxin also induces the production and release of proinflammatory cytokines from human macrophages. The macrophages were challenged with leukotoxin or lipopolysaccharide (LPS) from A. actinomycetemcomitans or LPS from Escherichia coli, and the production and secretion of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) were determined at the mRNA and protein levels by reverse transcription-PCR and enzyme-linked immunosorbent assay, respectively. Leukotoxin (1 to 30 ng/ml) induced abundant production and secretion of IL-1β, while the effects on IL-6 and TNF-α production were limited. Leukotoxin (1 ng/ml) caused a 10-times-higher release of IL-1β than did LPS (100 ng/ml). The secreted IL-1β was mainly the bioactive 17-kDa protein. At higher concentrations (>30 ng/ml), leukotoxin caused secretion of mainly inactive cytokine, the 31-kDa pro-IL-1β. The presence of specific antibodies to IL-1β or of a caspase 1 inhibitor blocked the secretion and production of the cytokine. Supernatants of leukotoxin-challenged macrophages stimulated bone resorption when tested in a mouse calvarial model. The activity could be blocked by an IL-1 receptor antagonist or specific antibodies to IL-1β. We concluded that A. actinomycetemcomitans leukotoxin can trigger abundant production and secretion of bioactive IL-1β by human macrophages, which is mediated by activation of caspase 1.

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Activation of Innate Immune Responses by Haemophilus influenzae Lipooligosaccharide

Clinical and Vaccine Immunology ◽

10.1128/cvi.00063-14 ◽

2014 ◽

Vol 21 (5) ◽

pp. 769-776 ◽

Cited By ~ 8

Author(s):

Joshua Choi ◽

Andrew D. Cox ◽

Jianjun Li ◽

William McCready ◽

Marina Ulanova

Keyword(s):

Haemophilus Influenzae ◽

Surface Expression ◽

Innate Immune ◽

Cell Surface Expression ◽

Necrosis Factor Alpha ◽

Content Type ◽

Hla Dr ◽

Proinflammatory Activity ◽

Factor Alpha ◽

Antigen Presenting

ABSTRACTA Gram-negative pathogenHaemophilus influenzaehas a truncated endotoxin known as lipooligosaccharide (LOS). Recent studies onH. influenzaeLOS highlighted its structural and compositional implications for bacterial virulence; however, the role of LOS in the activation of innate and adaptive immunity is poorly understood. THP-1 monocytes were stimulated with either lipopolysaccharide (LPS) fromEscherichia colior LOS compounds derived fromH. influenzaeEagan, Rd, and Rdlic1 lpsAstrains. Cell surface expression of key antigen-presenting, costimulatory, and adhesion molecules, as well as gene expression of some cytokines and pattern recognition receptors, were studied. Eagan and Rd LOS had a lower capacity to induce the expression of ICAM-1, CD40, CD58, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) compared to LPS. In contrast, antigen-presenting (HLA-ABC or HLA-DR) and costimulatory (CD86) molecules and NOD2 were similarly upregulated in response to LOS and LPS. LOS from a mutant Rd strain (Rdlic1 lpsA) consistently induced higher expression of innate immune molecules than the wild-type LOS, suggesting the importance of phosphorylcholine and/or oligosaccharide extension in cellular responses to LOS. An LOS compound with a strong ability to upregulate antigen-presenting and costimulatory molecules combined with a low proinflammatory activity may be considered a vaccine candidate to immunize againstH. influenzae.

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Trypanosoma cruzi Infects Human Dendritic Cells and Prevents Their Maturation: Inhibition of Cytokines, HLA-DR, And Costimulatory Molecules

Infection and Immunity ◽

10.1128/iai.67.8.4033-4040.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 4033-4040 ◽

Cited By ~ 72

Author(s):

Laurence Van Overtvelt ◽

Nathalie Vanderheyde ◽

Valérie Verhasselt ◽

Jamila Ismaili ◽

Louis De Vos ◽

...

Keyword(s):

Dendritic Cells ◽

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Human Monocyte ◽

Interleukin 12 ◽

Immune Functions ◽

Necrosis Factor Alpha ◽

Hla Dr ◽

Tnf Α

ABSTRACT Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas’ disease. Despite the many immune system disorders recognized in this infection and the crucial role played by dendritic cells (DC) in acquired immune responses, it was not known whether these cells could be infected by T. cruzitrypomastigotes and the consequences of such an infection on their immune functions. We now provide evidence that human monocyte-derived DC can be infected by T. cruzi and can support its intracellular multiplication. Interestingly, this infection has functional consequences on immature DC and on their maturation induced by lipopolysaccharide (LPS). First, after T. cruziinfection, the basal synthesis of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) was impaired. Furthermore, the process of maturation of DC induced by LPS was drastically affected by T. cruzi infection. Indeed, secretion of cytokines such as IL-12, TNF-α, and IL-6, which are released normally at high levels by LPS-activated DC, as well as the up-regulation of HLA-DR and CD40 molecules, was significantly reduced after this infection. The same effects could be induced by T. cruzi-conditioned medium, indicating that at least these inhibitory effects were mediated by soluble factors released by T. cruzi. Taken together, these results provide new insights into a novel efficient mechanism, directly involving the alteration of DC function, which might be used byT. cruzi to escape the host immune responses in Chagas’ disease and thus might favor persistent infection.

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Major Outer Membrane Protein Omp25 of Brucella suis Is Involved in Inhibition of Tumor Necrosis Factor Alpha Production during Infection of Human Macrophages

Infection and Immunity ◽

10.1128/iai.69.8.4823-4830.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 4823-4830 ◽

Cited By ~ 62

Author(s):

Véronique Jubier-Maurin ◽

Rose-Anne Boigegrain ◽

Axel Cloeckaert ◽

Antoine Gross ◽

Maria-Teresa Alvarez-Martinez ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Macrophage Infection ◽

Necrosis Factor Alpha ◽

Human Macrophages ◽

Tnf Α ◽

Brucella Suis ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Brucella spp. can establish themselves and cause disease in humans and animals. The mechanisms by whichBrucella spp. evade the antibacterial defenses of their host, however, remain largely unknown. We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-α) production upon human macrophage infection. This inhibition is associated with a nonidentified protein that is released into culture medium. Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production. Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis) on TNF-α production. For this purpose, omp25and omp31 null mutants of B. suis(Δomp25 B. suis and Δomp31 B. suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-α. We showed that, in contrast to WTB. suis or Δomp31 B. suis, Δomp25 B. suis induced TNF-α production when phagocytosed by human macrophages. The complementation of Δomp25 B. suis with WT omp25 (Δomp25-omp25 B. suis mutant) significantly reversed this effect: Δomp25-omp25 B. suis-infected macrophages secreted significantly less TNF-α than did macrophages infected with the Δomp25 B. suismutant. Furthermore, pretreatment of WT B. suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-α production during macrophage infection. These observations demonstrated that Omp25 of B. suis is involved in the negative regulation of TNF-α production upon infection of human macrophages.

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Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0267 ◽

2018 ◽

Vol 44 (4) ◽

pp. 530-538

Author(s):

Aysun Çetin ◽

İhsan Çetin ◽

Semih Yılmaz ◽

Ahmet Şen ◽

Göktuğ Savaş ◽

...

Keyword(s):

Oxidative Stress ◽

Interleukin 1 ◽

Paraoxonase 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phenotypic Effect ◽

Necrosis Factor Alpha ◽

Stress Markers ◽

Tnf Α ◽

Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

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Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽

10.3390/medicines5030106 ◽

2018 ◽

Vol 5 (3) ◽

pp. 106 ◽

Cited By ~ 4

Author(s):

Yuanjun Deng ◽

Kairui Tang ◽

Runsen Chen ◽

Yajie Liu ◽

Huan Nie ◽

...

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Low Dose ◽

Serum Levels ◽

Inflammatory Factors ◽

Enzyme Linked Immunosorbent Assay ◽

High Dose ◽

Model Group ◽

Necrosis Factor Alpha ◽

Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

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Angiography significantly decreased serum levels of IL-8 independent of artery stenosis

10.21203/rs.3.rs-119094/v1 ◽

2020 ◽

Author(s):

Lida Zare ◽

Akram Eidi ◽

Mohammad Safarian ◽

Mohammad Kazemi Arababadi

Keyword(s):

Protective Factor ◽

Serum Levels ◽

Artery Stenosis ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Before And After ◽

Elisa Technique ◽

Factor Alpha

Abstract Background Angiography is a safe cardiovascular technique for the diagnosis and treatment of the cardiovascular disorders. The potential effects of angiography on the cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are the important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of his project was to study the angiography effects on the serum levels of IL-8 and TNF-α. Methods Fifty-five participants in three groups, without, with one and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using enzyme linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-8, but not TNF-α, were significantly decreased following angiography. X-ray doses had moderate positive correlation with serum levels of TNF-α in the patients with more than one artery stenosis. Serum levels of IL-8 and TNF-α were not different among male and female participants in all groups. Discussion Angiography may be a protective factor for inflammation in IL-8 dependent manner. Using angiography in the patients with more than one artery stenosis needs to be executed cautiously.

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Guaiane-Type Sesquiterpenoids From Dendranthema morifolium (Ramat.) S. Kitam Flowers Protect H9c2 Cardiomyocyte From LPS-Induced Injury

Natural Product Communications ◽

10.1177/1934578x19864179 ◽

2019 ◽

Vol 14 (7) ◽

pp. 1934578X1986417

Author(s):

Beibei Zhang ◽

Mengnan Zeng ◽

Meng Li ◽

Wenjing Chen ◽

Benke Li ◽

...

Keyword(s):

Caspase 3 ◽

Creatine Phosphate ◽

Cardiomyocyte Apoptosis ◽

Exocyclic Double Bond ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Caspase 9 ◽

Necrosis Factor Alpha ◽

Thiazolyl Blue Tetrazolium Bromide ◽

Tnf Α

This study investigated the protective effects of guaiane-type sesquiterpenoids isolated from Dendranthema morifolium (Ramat.) S. Kitam ﬂowers on lipopolysaccharide (LPS)-induced injury in H9c2 cardiomyocyte. Cell viability was determined by thiazolyl blue tetrazolium bromide (MTT). The content of released tumor necrosis factor alpha (TNF- α) and interleukin 6 (IL-6) was evaluated by enzyme-linked immunosorbent assay. The levels of lactate dehydrogenase (LDH) and creatine phosphate kinase (CK) were measured by using commercial available kits. The protein expression levels of pelF2 α, GRP78, Bax, caspase-3, caspase-9, Bcl-2, LC3-II, and p62 were measured by in-cell Western. Flow cytometry was used to detect H9c2 cardiomyocyte apoptosis. Compounds 5, 7, 1, 8, and 2 exhibited the effects of cardioprotection and activity sequence enhancement. The levels of IL-6, TNF- α, LDH, CK, pelF2 α, GRP78, Bax, caspase-3, caspase-9, p62, and H9c2 cardiomyocyte apoptosis were increased in LPS-treated H9c2 cardiomyocyte, while those of Bcl-2 and LC3-II were decreased. These effects could be effectively reversed by compounds 5, 7, 1, 8, and 2. Results demonstrated that the guaiane-type sesquiterpenoids could prevent LPS-induced injury in cardiomyocyte by decreasing endoplasmic reticulum (ER) stress, apoptosis, and autophagy as well as downregulating the inflammatory mediators. In addition, the active groups of guaiane-type sesquiterpenoids might be the angelate at C-8 and the exocyclic double bond at C-11.

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Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension

Cephalalgia ◽

10.1177/0333102416650705 ◽

2016 ◽

Vol 37 (6) ◽

pp. 525-531 ◽

Cited By ~ 10

Author(s):

Bedia Samancı ◽

Yavuz Samancı ◽

Erdem Tüzün ◽

Güneş Altıokka-Uzun ◽

Esme Ekizoğlu ◽

...

Keyword(s):

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension ◽

Oligoclonal Bands ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Childbearing Age ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Tnf Α

Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1β, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1β level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1β ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1β, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.

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Early Local Cytokine Profiles in Strains of Mice with Different Outcomes from Chlamydial Genital Tract Infection

Infection and Immunity ◽

10.1128/iai.69.6.3556-3561.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 3556-3561 ◽

Cited By ~ 81

Author(s):

Toni Darville ◽

Charles W. Andrews ◽

James D. Sikes ◽

Patrick L. Fraley ◽

Roger. G. Rank

Keyword(s):

Proinflammatory Cytokines ◽

Genital Tract ◽

Host Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Genital Tract Infection ◽

Necrosis Factor Alpha ◽

Inflammatory Protein ◽

Tnf Α ◽

Genetically Determined ◽

Local Cytokine

ABSTRACT In this study, we expand on the examination of genetically determined differences in host responses that correlate with clearance of Chlamydia trachomatis from the genital tract. We infected C57BL/6, BALB/c, and C3H/HeN mice with the mouse pneumonitis agent of C. trachomatis (MoPn). C57BL/6 mice had the shortest course of infection (22 days) and the lowest incidence of severe hydrosalpinx. BALB/c mice also had a short course of infection (25 days), but all developed hydrosalpinx. C3H/HeN mice had the longest course of infection (38 days), and all developed severe hydrosalpinx. Determination of local cytokine responses by enzyme-linked immunosorbent assay (ELISA) of genital tract secretions revealed that the levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were significantly increased in the C57BL/6 and BALB/c strains compared to those in the C3H/HeN strain whereas the level of IL-6 was not different. The level of the neutrophil chemokine macrophage inflammatory protein 2 (MIP-2) was increased during the first week of infection in all three strains but was significantly higher in the BALB/c strain, the strain with the most rapid influx of neutrophils into the genital tract. Prolonged detection of MIP-2 in C3H/HeN mice was associated with a protracted presence of neutrophils in the genital tract. Early increases in the levels of the proinflammatory cytokines TNF-α and IL-1β are associated with earlier eradication of infection in the C57BL/6 and BALB/c strains than in the C3H/HeN strain. Increased levels of MIP-2 and neutrophils in BALB/c and C3H/HeN mice relative to C57BL/6 mice suggest that these responses may contribute to pathology.

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