scholarly journals TRPA1-mediated effects on the functional activity of macrophages under the exposure with cigarette smoke and cinnamaldehyde

2021 ◽  
pp. 28-36
Author(s):  
I. Yu. Sugaylo ◽  
D. E. Naumov ◽  
O. O. Kotova ◽  
D. A. Gassan, ◽  
Ya. G. Gorchakova
Keyword(s):  
Cigarette Smoke ◽  
Functional Activity ◽  
Phagocytic Activity ◽  
Phagocytic Cells ◽  
Experimental Conditions ◽  
Major Health Problem ◽  
Cell Responses ◽  
Mediated Effects ◽  
Tnf Α ◽  
A Minor

Introduction. Being the leading cause of COPD, smoking represents a major health problem. Upon entering the respiratory tract, cigarette smoke comes into contact with various cells, including macrophages expressing on their surface TRPA1 receptors, which are sensitive to the main pathogenic compounds formed during tobacco combustion.Aim. To study the functional activity of TRPA1 channels on macrophages in terms of cell responses to cigarette smoke and the TRPA1 agonist cinnamaldehyde (CA). Materials and methods. The experimental conditions included exposure of monocyte-derived macrophages to CA (100 μM), 4% cigarette smoke extract (CSE) and 4% CSE after pretreatment with TRPA1 selective antagonist (HC-030031 100 μM). The concentration of cytokines in the culture medium, the expression of TRPA1 on the cell surface, as well as the phagocytic activity of macrophages were analyzed by flow cytometry.Results. We found that 60.2 (49.6; 71.8)% of cells expressed TRPA1 and their number increased after exposure with CA. CSE significantly inhibited CXCL10 production from 1121.3 (295.7; 3154.6) pg/ml to 187.9 (113.8; 398.3) pg/ml (p=0.04), which was partially prevented by blocking TRPA1 (692.4 [428.6; 2916.6] pg/ml, p=0.04). Similar to CSE, CA also caused a decrease in CXCL10 concentration (189.2 [111.7; 311.3] pg/ml, p=0.03). Among other observations, there was an increase in the concentration of IL-1β after the exposition with HC-030031, as well as a decrease in TNF-α, IFN-γ and IL-12p70 after the treatment with CA. CSE caused a minor inhibition in phagocytic cells number, which was not prevented by TRPA1 blocking. CA, on the contrary, increased the phagocytic activity of macrophages. The initial expression of TRPA1 had a negative correlation with the dynamics of CXCL10 in response to CSE and CA but a positive correlation with the number of phagocytic cells after exposition with CA (ρ=0.81, p=0.005). Conclusions. TRPA1 expressed on macrophages apparently mediate an anti-inflammatory effect in terms of produced cytokines but increase phagocytic activity of the cells. TRPA1 are also major receptors involved in the diminished CXCL10 production by macrophage under exposition with cigarette smoke

scholarly journals Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function

2010 ◽  
Vol 78 (7) ◽  
pp. 3272-3279 ◽  
Author(s):  
Manuel Rodríguez-Zapata ◽  
Marlene J. Matías ◽  
Alfredo Prieto ◽  
Marco A. Jonde ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Phagocytic Activity ◽  
Human Brucellosis ◽  
Blood Monocytes ◽  
Phagocytic Cells ◽  
Necrosis Factor Alpha ◽  
Th1 Response ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-γ, IL-2, and TNF-α, but not that of IL-4, by phorbol myristate-activated CD4+ CD3+ and CD8+ CD3+ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-γ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.

Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

2019 ◽  
Vol 12 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Salvatore Benvenga ◽  
Antonio Micali ◽  
Giovanni Pallio ◽  
Roberto Vita ◽  
Consuelo Malta ◽  
...  
Keyword(s):  
Structural Changes ◽  
Natural Antioxidants ◽  
Minor Role ◽  
Positive Role ◽  
Testosterone Levels ◽  
Tnf Α ◽  
Testicular Lesions ◽  
A Minor ◽  
Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

scholarly journals Cigarette smoke inhalation aggravates diabetic kidney injury in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Songling Jiang ◽  
Do Van Quan ◽  
Jae Hyuck Sung ◽  
Moo-Yeol Lee ◽  
Hunjoo Ha
Keyword(s):  
Kidney Disease ◽  
Cigarette Smoke ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Smoke Inhalation ◽  
Lipoprotein Cholesterol ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Diabetic Kidney

Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg−1). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L−1), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.

scholarly journals Comparative Phenotypic and Functional Analyses of the Effects of IL-10 or TGF-β on Porcine Macrophages

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1098
Author(s):  
Tania Carta ◽  
Elisabetta Razzuoli ◽  
Floriana Fruscione ◽  
Susanna Zinellu ◽  
Dionigia Meloni ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Phagocytic Cells ◽  
Mhc Ii ◽  
Tnf Α ◽  
Regulated Expression ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Functional Analyses ◽  
The Impact ◽  
Immunosuppressive Cytokines

Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.

Suppression of human IL-1β, IL-2, IFN-γ, and TNF-α production by cigarette smoke extracts

2000 ◽  
Vol 106 (2) ◽  
pp. 280-287 ◽  
Author(s):  
Yanli Ouyang ◽  
Nisha Virasch ◽  
Ping Hao ◽  
Michael T. Aubrey ◽  
Neeta Mukerjee ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Tnf Α ◽  
Ifn Γ

Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow

2003 ◽  
Vol 284 (4) ◽  
pp. C977-C987 ◽  
Author(s):  
Monica M. Burdick ◽  
J. Michael McCaffery ◽  
Young S. Kim ◽  
Bruce S. Bochner ◽  
Konstantinos Konstantopoulos
Keyword(s):  
Cell Attachment ◽  
Carcinoma Cell ◽  
Umbilical Vein ◽  
Colon Adenocarcinoma ◽  
Rolling Velocity ◽  
Sialyl Lewis ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
A Minor ◽  
Sialylated Glycoproteins

This study was undertaken to investigate the molecular constituents mediating LS174T colon adenocarcinoma cell adhesion to 4-h TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) under flow. At 1 dyn/cm2, ∼57% of cells rolled and then became firmly adherent, whereas others continuously rolled on endothelium. Initial cell binding was primarily mediated by endothelial E-selectin. By using neuraminidase, glycolipid biosynthesis inhibitor d,l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol · HCl, trypsin, and flow cytometry, LS174T cells were shown to express sialyl Lewisx(sLex)- and di-sLex-decorated, but not sLea-decorated, glycolipid and glycoprotein ligands for E-selectin. The cells preferentially employed sialylated glycoproteins over glycolipids in adhesion as measured by conversion of rolling to firm adhesion, resistance to detachment by increased shear stress, and rolling velocity. However, a nonsialylated E-selectin counterreceptor also exists. Furthermore, LS174T α2, α6, and β1integrins support a minor pathway in adhesion to HUVECs. Finally, tumor cell attachment specifically increases HUVEC endocytosis of E-selectin. Altogether, the data indicate the complexity of carcinoma cell-endothelium adhesion via sialylated glycoconjugates, integrins, and their respective counterreceptors.

Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

2021 ◽  
Vol 30 (3) ◽  
pp. 109-126
Author(s):  
Laurent Poget ◽  
Catherine Goujon ◽  
Samuel Kleinhans ◽  
Serge Maeder ◽  
Jean-Pierre Schaller
Keyword(s):  
Cigarette Smoke ◽  
Heating System ◽  
Tobacco Product ◽  
Climatic Conditions ◽  
Mainstream Smoke ◽  
Humid Climate ◽  
Experimental Conditions ◽  
Puff Volume ◽  
Temperature And Humidity ◽  
Health Canada

Summary In order to assess robustness for the reduction of harmful and potentially harmful constituent (HPHC) levels generated by the Tobacco Heating System 2.2 (THS 2.2), a heated tobacco product, we compared the aerosol of this product with mainstream smoke from the 3R4F reference cigarette under different conditions of temperature and humidity. The desired climatic conditions were achieved by using an air-conditioning system coupled with the smoking-machine housing. Two extreme climatic conditions were selected, representing a “Hot and Dry” climate (30 °C and 35% relative humidity RH) and a “Hot and Very Humid” climate (30 °C and 75% RH). In addition, aerosol and smoke were generated using the standard conditions recognized for smoking-machine analyses of tobacco products (22 °C and 60% RH), which were close to the climatic conditions defined for “Subtropical and Mediterranean” environments (25 °C and 60% RH). The experimental conditions were chosen to simulate the use of THS 2.2 and cigarettes under extreme conditions of temperature and humidity. HeatSticks and cigarettes taken from freshly opened packs were subjected to short-term conditioning from two to a few more days under the same experimental conditions. We analyzed 54 HPHCs in THS 2.2 aerosol and 3R4F cigarette smoke, generated in accordance with the Health Canada Intense (HCI) standard, using modified temperature and humidity conditions for sample conditioning and machine-smoking experiments. We used a volume-adjusted approach for comparing HPHC reductions across the different climatic conditions investigated. Although a single puffing regimen was used, the total puff volume recorded for the 3R4F cigarette smoke varied due to the influence of temperature and humidity on combustion rate, which justified the use of a volume-adjusted approach. Volume-adjusted yields were derived from HPHC yields expressed in mass-per-tobacco stick normalized per total puff volume. The results indicated that, regardless of the considered climatic conditions, the HPHC levels investigated in THS 2.2 aerosol were reduced by at least 90%, on average, when compared with the concentrations in 3R4F cigarette mainstream smoke. This confirmed the robustness in performance for THS 2.2 to deliver reduced levels of HPHCs under the extreme climatic conditions investigated in this study. In order to further characterize the robustness of these reductions, the lowest reduction performance achieved for individual HPHCs across all climatic conditions was used to define the threshold for a robust reduction. The majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. Calculations derived from nicotine-adjusted yields also confirmed robust reductions for all investigated HPHCs. The small differences in absolute reduction between the volume- and nicotine-adjusted approaches were predominantly attributed to a combination of the differences in both nominal nicotine deliveries and total puff volumes between THS 2.2 and 3R4F cigarettes; however, this did not influence the determination of robustness. Our findings confirm the value of this approach for assessing the robustness of a product’s performance under different climatic conditions.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

scholarly journals Kinetics and Interplay of Mediators of Inflammation-Induced Bone Damage in the Course of Adjuvant Arthritis

2013 ◽  
Vol 26 (1) ◽  
pp. 37-48 ◽  
Author(s):  
S.M. Nanjundaiah ◽  
J.P. Stains ◽  
K.D. Moudgil
Keyword(s):  
Bone Remodeling ◽  
Inflammatory Cytokines ◽  
Adjuvant Arthritis ◽  
Bone Erosion ◽  
Experimental Conditions ◽  
Mediators Of Inflammation ◽  
Bone Damage ◽  
Tnf Α ◽  
Kinetics Of ◽  
Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-α are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-α and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1α, and GRO/KC), and between TNF-α and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.

scholarly journals Studies of the self-assembled growth mechanism on nanocrystalline silicon nanodots

2014 ◽  
Vol 6 (2) ◽  
Author(s):  
Samsudi Sakrani ◽  
Imam Sumpono ◽  
Nurul Aini Tarjudin ◽  
Zulkafli Othaman
Keyword(s):  
Self Assembly ◽  
Gas Flow ◽  
Nanocrystalline Silicon ◽  
Deposition Pressure ◽  
Experimental Conditions ◽  
Surface Energies ◽  
Corning Glass ◽  
Amorphous Si ◽  
A Minor ◽  
Solid Nucleation

Nanocrystalline silicon (nc-Si) nanodots have been grown on corning glass (7059) substrate using a self-assembly VHF-PECVD method under the following experimental conditions: Fixed deposition temperatures of 300/400 °C, deposition times 30/60 s, plasma power of 10 W, silane gas flow rate of 10 sccm, as well as deposition pressure of 10-2 torr. It is predicted that the onset of nucleation began immediately after the deposition and start to appear clearly after 20-60 s during which growth mechanisms occur. Essentially, the nanodots were formed onto the substrate in dome-like shapes by virtue of equilibrium surface energies, γLS, γLN andγNS. The associated liquid/solid nucleation mechanism was then simulated and related parameters were obtained: Free energy change per unit volume ΔGv ∼-104 Jmol-1; Surface energies per unit area, γLN = 1.44 Jm-2, γNS = 19 - 60 Jm-2 and γLS = 0.74 Jm-2; Critical energies ΔG* ∼10-15 J; Critical radii r* = 16 - 48 nm. These results were experimentally verified, in particular for selected critical radius r* less than 50 nm.Other measurements were also carried out: PL analysis gave bandgap energies ∼ 1.8-2.4 eV, whilst Raman spectra revealed the coexistence of nc-Si and amorphous Si. It is strongly suggested that, the nc-Si nanodot grown on glass substrate fulfills the Volmer-Weber growth mode with a minor modification.

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