scholarly journals The Anti-Pseudomonal Peptide D-BMAP18 Is Active in Cystic Fibrosis Sputum and Displays Anti-Inflammatory In Vitro Activity

2020 ◽  
Vol 8 (9) ◽  
pp. 1407
Author(s):  
Margherita Degasperi ◽  
Chiara Agostinis ◽  
Mario Mardirossian ◽  
Massimo Maschio ◽  
Andrea Taddio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Dnase I ◽  
Starting Point ◽  
Tnf Α ◽  
Specific Cytotoxicity ◽  
Ifn Γ ◽  
Lung Infections ◽  
Anti Inflammatory

Most Cystic Fibrosis (CF) patients succumb to airway inflammation and pulmonary infections due to Pseudomonas aeruginosa. D-BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, was evaluated as a possible antibacterial aimed to address this issue. The antipseudomonal activity of D-BMAP18 was tested in a pathophysiological context. The peptide displayed activity against CF isolates of Pseudomonas aeruginosa in the presence of CF sputum when combined with sodium chloride and DNase I. In combination with DNase I, D-BMAP18 discouraged the deposition of new biofilm and eradicated preformed biofilms of some P. aeruginosa strains. In addition, D-BMAP18 down regulated the production of TNF-α, IL1-β, and TGF-β in LPS-stimulated or IFN-γ macrophages derived from THP-1 cells indicating an anti-inflammatory activity. The biocompatibility of D-BMAP18 was assessed using four different cell lines, showing that residual cell-specific cytotoxicity at bactericidal concentrations could be abolished by the presence of CF sputum. Overall, this study suggests that D-BMAP18 may be an interesting molecule as a starting point to develop a novel therapeutic agent to simultaneously contrast lung infections and inflammation in CF patients.

Aspirin Blocks Orthodontic Relapse via Inhibition of CD4+ T Lymphocytes

2017 ◽  
Vol 96 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Y. Liu ◽  
T. Zhang ◽  
C. Zhang ◽  
S.S. Jin ◽  
R.L. Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Relapse Rate ◽  
Immune Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th1 Cells ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Ifn Γ ◽  
Anti Inflammatory

Immunologic response plays an important role in orthodontic tooth movement (OTM) and relapse. Nonsteroidal anti-inflammatory drugs, such as aspirin, affect immune cells and clinical orthodontic treatment. However, the mechanisms by which nonsteroidal anti-inflammatory drugs regulate immune cells to affect orthodontic relapse are unclear. In this study, male Sprague-Dawley rats were grouped as relapse and relapse + aspirin for 10 d after 14 d of OTM. Silicone impressions of the rats’ maxillary dentitions were obtained to record the distance of OTM at the indicated time point. CD4+ T lymphocytes in spleen were examined by flow cytometry. Serum levels of type 1 T-helper (Th1) cell–associated cytokines tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) were determined through enzyme-linked immunosorbent assay. The effects of aspirin on CD4+ T and Th1 cells were also analyzed in vitro. Aspirin treatment significantly reduced the relapse rate. More interestingly, injection of CD25 neutralizing antibody basiliximab or TNF-α inhibitor etanercept can significantly reduce the relapse rate as well. Correspondingly, aspirin treatment significantly accelerated the decrease of orthodontic force–induced secretion of TNF-α and IFN-γ in serum and the expression of TNF-α and IFN-γ in periodontal ligament during relapse. Furthermore, aspirin treatment in vitro significantly repressed the differentiation of CD4+ T and Th1 cells. Overall, results indicated that aspirin treatment can block orthodontic relapse by regulating Th1 cells.

scholarly journals Antioxidant and Inflammatory Effects of Nelumbo nucifera Gaertn. Leaves

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chong Li ◽  
Yongpeng He ◽  
Yue Yang ◽  
Yuting Gou ◽  
Shuting Li ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Animal Studies ◽  
Organ Index ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Kidney Liver ◽  
Lung And Kidney

This study is aimed at identifying the bioactive components in lotus leaf flavonoid extract (LLFE) and analyzing the antioxidant and anti-inflammatory activities of LLFE in vitro and in vivo. The flavonoids in LLFE were determined by UHPLC-MS/MS. The effect of LLFE on damaged 293T cells (H2O2, 0.3 mmol/L) was determined by MTT assay, and the activity of antioxidant enzymes was measured by kits. We studied the antioxidant and anti-inflammatory effects of LLFE on D-Gal/LPS (30 mg/kg·bw and 3 μg/kg·bw)-induced aging mice. We also evaluated the main organ index, pathological changes in the liver, lung, and kidney, liver function index, biochemical index, cytokine level, and mRNA expression level in serum and liver. The results showed that LLFE contains baicalein, kaempferol, kaempferid, quercetin, isorhamnetin, hyperoside, lespenephryl, and rutin. LLFE reduced the oxidative damage sustained by 293T cells, increased the levels of SOD, CAT, GSH, and GSH-Px, and decreased the level of MDA. The animal studies revealed that LLFE reduced oxidative damage and inflammation in injured mice, inhibited increases in AST, ALT, MDA, and NO, increased SOD, CAT, GSH, and GSH-Px levels, upregulated anti-inflammatory cytokines IL-10 and IL-12, and downregulated proinflammatory cytokines IL-6, IL-1β, TNF-α, and IFN-γ. Furthermore, the expression of antioxidant- and anti-inflammatory-related mRNA was consistent with the above results.

scholarly journals Use of a Multiplex Transcript Method for Analysis of Pseudomonas aeruginosa Gene Expression Profiles in the Cystic Fibrosis Lung

2016 ◽  
Vol 84 (10) ◽  
pp. 2995-3006 ◽  
Author(s):  
Alex H. Gifford ◽  
Sven D. Willger ◽  
Emily L. Dolben ◽  
Lisa A. Moulton ◽  
Dana B. Dorman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Expression Profiles ◽  
Clinical Isolates ◽  
Probe Design ◽  
Content Type ◽  
Lung Infections

The discovery of therapies that modulatePseudomonas aeruginosavirulence or that can eradicate chronicP. aeruginosalung infections associated with cystic fibrosis (CF) will be advanced by an improved understanding ofP. aeruginosabehaviorin vivo. We demonstrate the use of multiplexed Nanostring technology to monitor relative abundances ofP. aeruginosatranscripts across clinical isolates, in serial samples, and for the purposes of comparing microbial physiologyin vitroandin vivo. The expression of 75 transcripts encoded by genes implicated in CF lung disease was measured in a variety ofP. aeruginosastrains as well as RNA serial sputum samples from fourP. aeruginosa-colonized subjects with CF collected over 6 months. We present data on reproducibility, the results from different methods of normalization, and demonstrate high concordance between transcript relative abundance data obtained by Nanostring or transcriptome sequencing (RNA-Seq) analysis. Furthermore, we address considerations regarding sequence variation between strains during probe design. Analysis ofP. aeruginosagrownin vitroidentified transcripts that correlated with the different phenotypes commonly observed in CF clinical isolates.P. aeruginosatranscript profiles in RNA from CF sputum indicated alginate productionin vivo, and transcripts involved in quorum-sensing regulation were less abundant in sputum than strains grown in the laboratory.P. aeruginosagene expression patterns from sputum clustered closely together relative to patterns for laboratory-grown cultures; in contrast, laboratory-grownP. aeruginosashowed much greater transcriptional variation with only loose clustering of strains with different phenotypes. The clustering within and between subjects was surprising in light of differences in inhaled antibiotic and respiratory symptoms, suggesting that the pathways represented by these 75 transcripts are stable in chronic CFP. aeruginosalung infections.

scholarly journals Pseudomonas aeruginosa Volatilome Characteristics and Adaptations in Chronic Cystic Fibrosis Lung Infections

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Trenton J. Davis ◽  
Ava V. Karanjia ◽  
Charity N. Bhebhe ◽  
Sarah B. West ◽  
Matthew Richardson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Chemical Diversity ◽  
Chronic Infections ◽  
Lung Function Decline ◽  
Content Type ◽  
Flight Mass Spectrometry ◽  
Patient Health ◽  
Lung Infections

ABSTRACT Pseudomonas aeruginosa chronic lung infections in individuals with cystic fibrosis (CF) significantly reduce quality of life and increase morbidity and mortality. Tracking these infections is critical for monitoring patient health and informing treatments. We are working toward the development of novel breath-based biomarkers to track chronic P. aeruginosa lung infections in situ. Using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC–TOF-MS), we characterized the in vitro volatile metabolomes (“volatilomes”) of 81 P. aeruginosa isolates collected from 17 CF patients over at least a 5-year period of their chronic lung infections. We detected 539 volatiles produced by the P. aeruginosa isolates, 69 of which were core volatiles that were highly conserved. We found that each early infection isolate has a unique volatilome, and as infection progresses, the volatilomes of isolates from the same patient become increasingly dissimilar, to the point that these intrapatient isolates are no more similar to one another than to isolates from other patients. We observed that the size and chemical diversity of P. aeruginosa volatilomes do not change over the course of chronic infections; however, the relative abundances of core hydrocarbons, alcohols, and aldehydes do change and are correlated with changes in phenotypes associated with chronic infections. This study indicates that it may be feasible to track P. aeruginosa chronic lung infections by measuring changes to the infection volatilome and lays the groundwork for exploring the translatability of this approach to direct measurement using patient breath. IMPORTANCE Pseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF), which are correlated with lung function decline. Significant clinical efforts are therefore aimed at detecting infections and tracking them for phenotypic changes, such as mucoidy and antibiotic resistance. Both the detection and tracking of lung infections rely on sputum cultures, but due to improvements in CF therapies, sputum production is declining, although risks for lung infections persist. Therefore, we are working toward the development of breath-based diagnostics for CF lung infections. In this study, we characterized of the volatile metabolomes of 81 P. aeruginosa clinical isolates collected from 17 CF patients over a duration of at least 5 years of a chronic lung infection. We found that the volatilome of P. aeruginosa adapts over time and is correlated with infection phenotype changes, suggesting that it may be possible to track chronic CF lung infections with a breath test.

scholarly journals Peptide dendrimers as “lead compounds” for the treatment of chronic lung infections by Pseudomonas aeruginosa in cystic fibrosis patients: in vitro and in vivo studies

2018 ◽  
Vol Volume 11 ◽  
pp. 1767-1782 ◽  
Author(s):  
Arianna Pompilio ◽  
Cristina Geminiani ◽  
Paolo Mantini ◽  
Thissa N Siriwardena ◽  
Ivan Di Bonaventura ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
In Vivo Studies ◽  
Lead Compounds ◽  
Peptide Dendrimers ◽  
Lung Infections

scholarly journals γδ T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-α and IFN-γ-producers in response to Pseudomonas aeruginosa

2003 ◽  
Vol 4 (1) ◽  
Author(s):  
Salvador Raga ◽  
M Rosa Julià ◽  
Catalina Crespí ◽  
Joan Figuerola ◽  
Natalia Martínez ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
T Lymphocytes ◽  
Healthy Donors ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals PSEUDOMONAS AERUGINOSA VOLATILOME CHARACTERISTICS AND ADAPTATIONS IN CHRONIC CYSTIC FIBROSIS LUNG INFECTIONS

2020 ◽  
Author(s):  
Trenton J. Davis ◽  
Ava V. Karanjia ◽  
Charity N. Bhebhe ◽  
Sarah B. West ◽  
Matthew Richardson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Chemical Diversity ◽  
Chronic Infections ◽  
Flight Mass Spectrometry ◽  
Detection And Tracking ◽  
Sputum Production ◽  
Patient Health ◽  
Lung Infections

ABSTRACTPseudomonas aeruginosa chronic lung infections in individuals with cystic fibrosis (CF) significantly reduce quality of life and increase morbidity and mortality. Tracking these infections is critical for monitoring patient health and informing treatments. We are working toward the development of novel breath-based biomarkers to track chronic P. aeruginosa lung infections in situ. Using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS), we characterized the in vitro volatile metabolomes (or volatilomes) of 81 P. aeruginosa isolates collected from 17 CF patients over at least a five-year period of their chronic lung infections. We detected 539 volatiles produced by the P. aeruginosa isolates, 69 of which were core volatiles that were highly conserved. We found that each early infection isolate has a unique volatilome, and as infection progresses, the volatilomes of isolates from the same patient become increasingly dissimilar, to the point that these intra-patient isolates are no more similar to one another than to isolates from other patients. We observed that the size and chemical diversity of P. aeruginosa volatilomes do not change over the course of chronic infections; however, the relative abundances of core hydrocarbons, alcohols, and aldehydes do change, and are correlated to changes in phenotypes associated with chronic infections. This study indicates that it may be feasible to track P. aeruginosa chronic lung infections by measuring changes to the infection volatilome, and lays the groundwork for exploring the translatability of this approach to direct measurement using patient breath.IMPORTANCEPseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF), and are correlated with lung function declines. Significant clinical efforts are, therefore, aimed at detecting infections and tracking them for phenotypic changes, such as mucoidy and antibiotic resistance. Both the detection and tracking of lung infections relies on sputum cultures, but due to improvements in CF therapies, sputum production is declining though risks for lung infections persist. Therefore, we are working toward the development of breath-based diagnostics for CF lung infections. In this study we characterized of the volatile metabolomes of 81 P. aeruginosa clinical isolates collected from 17 CF patients over a duration of at least five years of a chronic lung infection. We found that the volatilome of P. aeruginosa adapts over time, and correlates to infection phenotype changes, suggesting it may be possible to track chronic CF lung infections with a breath test.

scholarly journals Αλληλεπίδραση μεταβιβαστών φλεγμονής και κυτταρικών πληθυσμών του αναπνευστικού επιθηλίου στην παθογένεια της ιδιοπαθούς πνευμονικής ίνωσης

2018 ◽  
Author(s):  
Ευάγγελος Μπούρος
Keyword(s):  
Real Time ◽  
Tissue Factor ◽  
Real Time Pcr ◽  
Dnase I ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ

Η Ιδιοπαθής Πνευμονική Ίνωση (IPF/ΙΠΙ) χαρακτηρίζεται από βλάβη του κυψελιδικού επιθηλίου, ρήξη της βασικής μεμβράνης και απορρύθμιση του επουλωτικού μηχανισμού με κυρίαρχο ρόλο να έχουν οι μυοϊνοβλάστες, κύτταρα αποκλειστικά υπεύθυνα για την υπερβολική παραγωγή και εναπόθεση κολλαγόνου στο πνευμονικό παρέγχυμα, που έχει ως αποτέλεσμα την αναδιαμόρφωσή του (remodeling). Αν και τα τελευταία χρόνια υπάρχει εντατική έρευνα σε ότι αφορά την κατανόηση των μηχανισμών που οδηγούν σε αυτή, παραμένουν πολλά ανεξερεύνητα μονοπάτια της παθογένεια της.Σκοπός της παρούσας μελέτης είναι η διερεύνηση του ρόλου των υποεπιθηλιακών μυοϊνοβλαστών του πνεύμονα (ΥΜΠ) και των διαλυτών μεσολαβητικών παραγόντων που επιδρούν στην ενεργοποίησή τους και την ανάπτυξη της ίνωσης σε ασθενείς με ιδιοπαθή πνευμονική ίνωση.Για το σκοπό της μελέτης ελήφθη βρογχοκυψελιδικό έκπλυμα (ΒΚΕ) χρησιμοποιώντας το εύκαμπτο βρογχοσκόπιο με την καθιερωμένη τεχνική από ασθενείς με γνωστή ΙΠΙ βάσει των ισχυόντων διαγνωστικών κριτηρίων (ATS/ERS/JRS/ALAT 2011). Για ομάδα ελέγχου χρησιμοποιήθηκε ΒΚΕ από ασθενείς με ιδιοπαθή μη ειδική διάμεση πνευμονία (iNSIP), πάθηση η οποία ανήκει μεν στις ιδιοπαθείς διάμεσες πνευμονίες, όμως είναι διακριτή ως προς την παθογένεια, την πορεία και θεραπεία της, καθώς και από φυσιολογικά άτομα τα οποία υποβλήθηκαν σε βρογχοσκόπηση για διαγνωστικούς λόγους. Οι ΥΜΠ απομονώθηκαν από χειρουργικά δείγματα υγιούς πνευμονικού ιστού τα οποία στη συνέχεια καλλιεργήθηκαν με προ-φλεγμονώδεις παράγοντες ή με ΒΚΕ από ασθενείς με IPF ή iNSIP και εκτιμήθηκε η ινωτική τους δράση με την δοκιμασία επούλωσης τραύματος, in vitro, με διαδοχική λήψη εικόνων μέσω ανάστροφου μικροσκοπίου Olympus, καθώς και με την παραγωγή κολλαγόνου (μg/mL). H απομόνωση του ολικού RNA έγινε με την χρήση του TRIzol και ο καθαρισμός του με τη χρήση του κιτ DNase I. Η έκφραση των ινωτικών παραγόντων Tissue factor (ΤF) και (TNF-like ligand 1A) TL1A από τους ΥΜΠ έγινε με real time PCR. Παράλληλα μελετήθηκε ο ρόλος των διαλυτών μεσολαβητών IL-1α, TNF-α και IFN-γ είτε μόνων είτε σε συνδυασμό, στην προαγωγή και έκφραση των ινωτικών παραγόντων, ιστικού παράγοντα (tissue factor, TF), TGF-β και TL1A από τους ΥΜΠ. Για την ποσοτικοποίησή τους χρησιμοποιήθηκε η τεχνική της RT-PCR μετά από σύνθεση του cDNA. O χαρακτηρισμός των μυοϊνοβλαστών και η εντόπιση του TL1A έγιναν με την τεχνική του ανοσοφθορισμού. Η έκφραση των ινωτικών παραγόντων TF και TL1A, καθώς και η παραγωγή κολλαγόνου από τους ΥΜΠ έγινε με RT-PCR και Sircol assay, αντιστοίχως. Από την παρούσα μελέτη προέκυψαν τα εξής αποτελέσματα. Διέγερση των ΥΜΠ με ΒΚΕ, ασθενών και μη (n=3), ή μαζί με τη προσθήκη συνδυασμού κυτταροκινών (IL-1α+TNF-α+IFN-γ) υπήρξε στατιστικά σημαντική αύξηση επιπέδου κολλαγόνου (IPF1: 183.99 μg/ml±14.03, p<0.01, IPF2: 118.50 μg/ml±5.04, p<0.05, IPF3: 126.23 μg/ml±2.7, p<0.05 και 3C: 184.72 μg/ml±29.72, p<0.05 σε σύγκριση με τα μη διεγερμένα: 63 μg/ml±1.2). Διέγερση των ΥΜΠ με ΒΚΕ, ασθενών και μη, ή μαζί με προ-φλεγμονώδεις κυτταροκίνες (IL-1α, TNF-α) έδειξε μια στατιστικά σημαντική αύξηση στη μεταγραφική ενεργότητα του TF (IPF: 3.56-fold±0.14, IL-1α: 2.5-fold±0.08, TNF-α: 2.3-fold±0.007, 2C: 2.7-fold±0.17, p<0.05 σε σύγκριση με τα μη διεγερμένα: 1.1-fold±0.3) και TL1A (IPF: 6.5-fold±0.8, IL-1α: 156-fold±14.94, TNF-α: 240-fold±7.8, 2C: 116-fold±3.6, p<0.01 σε σύγκριση με τα μη διεγερμένα: 1.3-fold±0.6). Τα επίπεδα του TL1A επιβεβαιώθηκαν με ανοσοφθορισμό. Είναι η πρώτη φορά που ο TL1A ερευνάται στους ΥΜΠ. Διέγερση των ΥΜΠ μαζί με προ-φλεγμονώδεις κυτταροκίνες δεν επέδειξε κάποια σημαντική αύξηση στη μεταναστευτική ικανότητα σε σύγκριση με αυτή που διεγέρθηκαν με ΒΚΕ (IPF2: 43.69%±2.16, p<0.01, IPF3: 36.49%±2.37, p<0.05).Συμπερασματικά, το BALF από ασθενείς με ΙΠΙ επάγει την ινωτική δραστηριότητα σε μυοϊνοβλάστες πνεύμονα, παρόμοιο με τους μεσολαβητές που σχετίζονται με την ίνωση του πνεύμονα, υποδεικνύοντας έναν βασικό ρόλο των ΥΜΠ στην ΙΠΙ. Η κυτταροκίνη TL1A είναι μία σημαντική ινωτική κυτταροκίνη, που εκλύεται αρκετά στις ινωτικές βλάβες και επιδρά στην ινωτική δραστηριότητα των μυοϊνοβλαστών των ασθενών με ΙΠΙ.

scholarly journals Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation

2020 ◽  
Vol 48 (5-6) ◽  
pp. 252-267 ◽  
Author(s):  
Julia Katharina Metz ◽  
Birgit Wiegand ◽  
Sabrina Schnur ◽  
Katharina Knoth ◽  
Nicole Schneider-Daum ◽  
...  
Keyword(s):  
Barrier Function ◽  
Barrier Properties ◽  
In Vitro Test ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
The Impact

The incidence of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) remains an important problem, particularly in the present time with the Covid-19 pandemic. However, an adequate in vitro test system to monitor the barrier function of the alveolar epithelium during inflammation and for assessing anti-inflammatory drugs is urgently needed. Therefore, we treated human Alveolar Epithelial Lentivirus-immortalised cells (hAELVi cells) with the pro-inflammatory cytokines TNF-α (25 ng/ml) and IFN-γ (30 ng/ml), in the presence or absence of hydrocortisone (HC). While TNF-α and IFN-γ are known to reduce epithelial barrier properties, HC could be expected to protect the barrier function and result in an anti-inflammatory effect. We investigated the impact of anti-inflammatory/inflammatory treatment on transepithelial electrical resistance (TEER) and the apparent permeability coefficient (P app) of the low permeability marker sodium fluorescein (NaFlu). After incubating hAELVi cells for 48 hours with a combination of TNF-α and IFN-γ, there was a significant decrease in TEER and a significant increase in the P app. The presence of HC maintained the TEER values and barrier properties, so that no significant P app change was observed. By using hAELVi cells to study anti-inflammatory drugs in vitro, the need for animal experiments could be reduced and pulmonary drug development accelerated.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

Sign in / Sign up

Export Citation Format

Share Document