scholarly journals Characterizing Inflammatory Cell Asthma Associated Phenotypes in Dental Health Workers Using Cytokine Profiling

2021 ◽  
Vol 2 ◽  
Author(s):  
Tanusha Singh ◽  
Braimoh Bello ◽  
Mohamed F. Jeebhay

Cytokines elicit a pro-inflammatory response by modifying the airway microenvironment in patients with acute or chronic asthma. The expression pattern of several distinct cytokines could be a useful discriminator in asthma. This study aimed to identify asthma subject groupings based on common inflammatory patterns and to determine the relationship between these identified patterns and asthma-associated clinical indices. A sub-group of 76 dental healthcare workers (HCWs) identified from a larger cross-sectional study of 454 dental HCWs in five dental institutions were evaluated further. A self-administered questionnaire elicited the health and employment history of subjects. Sera were analyzed for atopic status, latex sensitization, and 12 cytokines (IL-1β, 3, 4, 5, 6, 7, 8, 10, 12p70, eotaxin, GM-CSF, TNF-α). Pre and post-bronchodilator spirometry was performed on all HCWs. Data clustering and factor analysis were used to identify inflammatory cluster patterns of cytokines. Associations between the cytokine cluster groupings and relevant asthma-associated clinical indices were determined using multivariate logistic regression. The classification of asthma subtype based on cytokine patterns demonstrated both eosinophilic and neutrophilic inflammatory responses. Four phenotypically distinct subgroups relating to the severity of inflammation (acute or chronic) of the cell types were identified. Cytokine determinants for the neutrophilic subtype included IL-1β, 6, 8, 10, 12p70, and TNF-α whereas for the eosinophilic subtype these included IL-3, 4, 5, 7, eotaxin, and GM-CSF. The multivariate models showed a significant association between work-related chest symptoms and all four inflammatory patterns. However, stronger associations were observed for the acute neutrophilic (OR = 6.00, p < 0.05) compared to acute and chronic eosinophilic responses (OR = 4.30, p < 0.05; OR = 4.93, p < 0.05), respectively. Subjects with airway obstruction were more likely to have a mixed cellular infiltrate. The odds of work-exacerbated asthma were increased in acute or chronic eosinophilia (OR = 7.75 and 8.12; p < 0.05), respectively as well as with acute neutrophilia (OR = 6) sub-type. This study demonstrated that neutrophilic inflammatory cell asthma phenotypes coexist with eosinophilic inflammatory phenotypes suggesting a possible dual pathway for asthma in dental health workers, probably due to mixed exposures to high molecular weight (e.g., latex) and low molecular weight (e.g., acrylates) agents.

2013 ◽  
Vol 304 (6) ◽  
pp. F737-F750 ◽  
Author(s):  
David A. Vesey ◽  
Jacky Y. Suen ◽  
Vernon Seow ◽  
Rink-Jan Lohman ◽  
Ligong Liu ◽  
...  

Protease-activated receptor-2 (PAR2) is a G protein-coupled receptor abundantly expressed in the kidney. The aim of this study was to profile inflammatory gene and protein expression induced by PAR2 activation in human kidney tubular epithelial cells (HTEC). A novel PAR2 antagonist, GB88, was used to confirm agonist specificity. Intracellular Ca2+ (iCa2+) mobilization, confocal microscopy, gene expression profiling, qRTPCR, and protein expression were used to characterize PAR2 activation. PAR2 induced a pronounced increase in iCa2+ concentration that was blocked by the PAR2 antagonist. Treatment with SLIGKV-NH2 at the apical or basolateral cell surface for 5 h induced expression of a range of inflammatory genes by greater than fourfold, including IL-1β, TRAF1, IL-6, and MMP-1, as assessed by cDNA microarray and qRTPCR analysis. Using antibody arrays, GM-CSF, ICAM-1, TNF-α, MMP-1, and MMP-10 were among the induced proteins secreted. Cytokine-specific ELISAs identified three- to sixfold increases in GM-CSF, IL-6, IL-8, and TNF-α, which were blocked by GB88 and protein kinase C inhibitors. Treatment of cells at the basolateral surface induced more potent inflammatory responses, with release of MCP-1 and fibronectin to the apical and basolateral compartments; apical treatment only increased secretion of these factors to the apical compartment. PAR2 activation at the basolateral surface dramatically reduced transepithelial electrical resistance (TEER) whereas apical treatment had no effect. There was very little leakage (<5%) of peptides across the cell monolayer (liquid chromatography-mass spectrometry). In summary, SLIGKV-NH2 induced robust proinflammatory responses in HTEC that were antagonized by GB88. These results suggest that PAR2 antagonists could be useful disease-modifying, anti-inflammatory agents in kidney disease.


2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Indra Cahyadinata ◽  
Indasah Indasah ◽  
Sandu Siyoto

Dental health personnel in carrying out daily care can not be separated from contact with saliva and blood which can be an intermediary in the spread of cross infection. Cross infection is common in medical treatment procedures including dental and oral care. Prevention of cross infection needs to be done to avoid transmission of disease from medical procedures to patients and dental health workers. The purpose of this study was to determine the factors that influence the compliance of the dentist Koas to the application of the Precaution Standard at RSGM IIK BW Kediri. The method in this study was observational descriptive with cross-sectional design. The number of samples is 67 Koas dentists using the Slovin formula. The tools and materials used in the research are check list sheets and stationery. The data processing in this study uses the SPSS program by using a binary logistic test. The results of this study indicate that from several factors that influence the compliance of dentist councils in applying the precaution standard at RSGM IIK BW Kediri is a knowledge factor of p = 0.010 (<0.005), supervision is p = 0.003 (<0.005), and the availability of infrastructure is p = 0.006 (<0.005) with supervisory variables which are the variables that have the most individual influence compared to the other variables. Thus in drawing the conclusion that the level of knowledge, supervision and facilities and infrastructure is a factor that influences the compliance of dentists in implementing the implementation of precaution standards that have been set for prevention of cross infection.


2021 ◽  
Author(s):  
Bo Mi Lee ◽  
Sang Jun Park ◽  
Insup Noh ◽  
Chun-Ho Kim

Abstract Background: The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages. Methods: The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (100 μg/mL) or high (100 μg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.Results: Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241±161, 96,531±1,167, 512,657±8,545, and 1,249,500±37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 μg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45%. Using NanoString technology, we also found that the immune-related genes TNF‐α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 μg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.Conclusions: High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 460 ◽  
Author(s):  
Tracy L Rimington ◽  
Emily Hodge ◽  
Charlotte K Billington ◽  
Sangita Bhaker ◽  
Binaya K C ◽  
...  

Background: Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. Method: Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM).  Inflammatory responses were assessed using Luminex analysis of tissue culture supernatants to measure levels of 21 chemokines, growth factors and cytokines. Results: A robust and reproducible inflammatory signal was detected across all donors for 12 of the analytes measured following LPS stimulation with a modest fold increase (<2-fold) in levels of CCL22, IL-4, and IL-2; increases of 2-4-fold in levels of CXCL8, VEGF and IL-6 and increases >4-fold in CCL3, CCL4, GM-CSF, IL-10, TNF-α and IL-1β.  The inflammatory signal induced by IL-1β stimulation was less than that observed with LPS but resulted in elevated levels of 7 analytes (CXCL8, CCL3, CCL4, GM-CSF, IL-6, IL-10 and TNF-α).  The inflammatory responses induced by both stimulations was supressed by dexamethasone for the majority of analytes. Conclusions: These data provide proof of concept that this ex vivo human lung explant model is responsive to inflammatory signals and could be used to investigate the anti-inflammatory effects of existing and novel compounds.  In addition this model could be used to help define the mechanisms and pathways involved in development of inflammatory airway disease. Abbreviations: COPD: Chronic Obstructive Pulmonary Disease; ICS: inhaled corticosteroids; LPS: lipopolysaccharide; IL-1β: interleukin-1 beta; PSF: penicillin, streptomycin and fungizone


2002 ◽  
Vol 13 (12) ◽  
pp. 4497-4507 ◽  
Author(s):  
Hebin Liu ◽  
Thomas Grundström

The multipotent cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) is involved in particular in the physiological response to infection and in inflammatory responses. GM-CSF is produced by many cell types, including T lymphocytes responding to T-cell receptor activation and mantle zone B lymphocytes. B-cell receptor and T-cell receptor activation generates two major signals: an increase in intracellular Ca2+concentration and a protein kinase cascade. Previous studies have shown that the Ca2+/calmodulin-dependent phosphatase calcineurin mediates stimulation of GM-CSF transcription in response to Ca2+. In this study, we show that Ca2+signaling also regulates GM-CSF transcription negatively through Ca2+/calmodulin-dependent kinase II (CaMK II) phosphorylation of serines in the autoinhibitory domain for DNA binding of the transcription factor Ets1. Wild-type Ets1 negatively affects GM-CSF transcription on Ca2+stimulation in the presence of cyclosporin A, which inhibits calcineurin. Conversely, Ets1 with mutated CaMK II target serines showed an increase in transactivation of the GM-CSF promoter/enhancer. Moreover, constitutively active CaMK II inhibited transactivation of GM-CSF by wild-type Ets1 but not by Ets1 with mutated CaMK II sites. Mutation of CaMK II target serines in Ets1 also relieves inhibition of cooperative transactivation of GM-CSF with the Runx1/AML1 transcription factor. In addition, the Ca2+-dependent phosphorylation of Ets1 reduces the binding of Ets1 to the GM-CSF promoter in vivo.


2017 ◽  
Vol 1 (S1) ◽  
pp. 30-30
Author(s):  
Mary S. Rodriguez-Rabassa ◽  
Kaumudi Joshipura Jinraj ◽  
Maribel Campos Rivera ◽  
Vasiliki Michopoulos ◽  
Yasuhiro Yamamura

OBJECTIVES/SPECIFIC AIMS: Childhood obesity has become an issue of some concern worldwide. Some reviews and a recent study in adults have indicated that obesity-related inflammatory responses produce brain damage. However, studies exploring associations between inflammation and executive functions in children are overlooked. Therefore, the objective of this cross-sectional study is to determine whether difficulties in executive functions and emotional processing are associated with obesity and inflammation. METHODS/STUDY POPULATION: We have recruited 12 of a total of 60 children aged 6–8 years old. They have completed the NIH Toolbox Cognition Battery and the NEPSY II Affect Recognition tests. Samples of plasma and saliva were collected to quantify inflammatory biomarkers cytokines (IL-6 and TNF-α) assay by Luminex procedure. We performed descriptive analysis and Mann-Whitney U test to compare obese Versus nonobese groups. RESULTS/ANTICIPATED RESULTS: Obese children have lower scores in measures of affect recognition than healthy weight children. They also showed higher median scores in both salivary and plasma IL-6 and TNF-α. DISCUSSION/SIGNIFICANCE OF IMPACT: Although no statistical differences were found among groups in either measurement, these preliminary data based on the initial recruitment suggest that children with higher body mass index may have difficulties in emotional processing. More data will be available after completing recruitment to determine if the association between obesity and affect recognition is significant and if it is mediated by inflammation.


2006 ◽  
Vol 101 (5) ◽  
pp. 1394-1399 ◽  
Author(s):  
Jennifer M. Peterson ◽  
Kevin D. Feeback ◽  
Joel H. Baas ◽  
Francis X. Pizza

Tumor necrosis factor-α (TNF-α) has been associated with cachexia and is known to regulate multiple inflammatory cell (neutrophil and macrophage) responses. We tested the hypothesis that neutrophils and macrophages accumulate in the extensor digitorum longus (EDL) and soleus muscles of mice after chronic TNF-α administration. Murine recombinant TNF-α (∼100 μg·kg−1·day−1) in vehicle solution or vehicle solution alone (sham) was administered to C57BL/6 mice for 7 days via osmotic minipumps. In EDL muscles from TNF-α-treated mice, neutrophil and macrophage concentrations were elevated seven- and threefold, respectively, compared with sham mice. Neutrophil and macrophage concentrations were also elevated five- and twofold, respectively, in solei of TNF-α- relative to sham-treated mice. Treatment with TNF-α elevated ubiquitin content by ∼25% relative to sham values for both the EDL and soleus muscles; however, these elevations were not statistically significant. No differences were observed between TNF-α- and sham-treated mice in body weight, food consumption, muscle mass, myofiber cross-sectional area, carbonyl groups, total protein content, or relative abundance of myosin heavy chain protein. Furthermore, no overt signs of muscle injury or regeneration were observed in muscles from TNF-α-treated mice in either the EDL or soleus muscles. These observations suggest that 7 days of TNF-α administration promote muscle inflammation as indicated by the accumulation of neutrophils and macrophages without overt signs of atrophy, injury, or regeneration.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Somsiri Decharat ◽  
Piriyalux Phethuayluk ◽  
Supandee Maneelok

Objectives. The objective of this study was to describe the socioeconomic situation of dental health work and work characteristics and to evaluate the prevalence of musculoskeletal symptoms among dental health workers.Material and Methods. A cross-sectional study was conducted with 124 dental health workers and 124 persons in the reference group, matched to dental health workers by gender, were recruited from the workers who worked at the same 17 community hospitals in Nakhon Si Thammarat province, Thailand. Information was collected by using questionnaire. Data analysis comprised descriptive and analytical components.Results and Discussion. 75.8% were female and 24.2% were male dental health workers. 91.9% of subjects had worked >5 years. Most subjects worked for >8 hours per day and worked >6 days per week, at 63.7% and 53.2%, respectively. 100% of subjects worked in public institutions, and 68% also worked in both public and private institutions. Most subjects (52.4%) did not exercise. Daily activity, gender, duration of work, hours worked per day, days worked per week, and physical activity were significantly associated with musculoskeletal symptoms at <0.001.Conclusion. The prevention and reduction of MSDs among dentists should include improving their education in dental ergonomics.


2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Bo Mi Lee ◽  
Sang Jun Park ◽  
Insup Noh ◽  
Chun-Ho Kim

Abstract Background The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages. Methods The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1 H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (10 µg/mL) or high (100 µg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR. Results Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241 ± 161, 96,531 ± 1,167, 512,657 ± 8,545, and 1,249,500 ± 37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 µg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45 %. Using NanoString technology, we also found that the immune-related genes TNF-α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 µg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages. Conclusions High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.


2018 ◽  
Vol 12 (1) ◽  
pp. 32
Author(s):  
Nova Herawati ◽  
Fitri Agusni ◽  
Ika Ifitri

Dental  health workers have a high risk infection because the presence of pathogenic microorganisms in the oral cavity including blood and saliva and possibility of injury caused by needle stick. Transmission of infection can be prevented by reducing contact with cause of infection one of them with the use of self-protection tool in according “Standard Operational Procedure”. The study aim is to know the Knowledge of Dental Nurses about Infectious Diseases against the Use of Personal Protection Equipment in Dental Policlinic of Puskesmas in Bukittinggi and Payakumbuh. By using “Cross Sectional” design. Population was used all dental nurse at Dental Clinic amount 30 peoples. By using total population and data collection using questionnaire and observation. The results is a positive relationship and stronger between the knowledge of dental nurse about infection diseases of the using self-protection tool with r value in the amount of 0,886 (α 0,00 < 0,05). The conclusion is the higher knowledge of dental nurses about infectious diseases will be more complete and appropriate SOP. Suggested can be increasing their knowledge about infectious disease so that can protect him self one of them with the use of self-protection equipment according to SOP before and during the action.


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