Eosinophil Recruiting Chemokines are Down-Regulated in Peripheral Blood Mononuclear Cells of Allergic Patients Treated with Deflazocort or Desloratadine

2007 ◽  
Vol 20 (4) ◽  
pp. 745-751 ◽  
Author(s):  
M.B. Di Sciascio ◽  
G. Vianale ◽  
N. Verna ◽  
C. Petrarca ◽  
A. Perrone ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
Allergic Inflammation ◽  
Persistent Asthma ◽  
Mrna Levels ◽  
Receptor Antagonists ◽  
Peripheral Blood Mononuclear ◽  
Asthmatic Patients ◽  
Before And After ◽  
Pre Treatment

Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophil/basophil activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic/asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, 1–309 (CCL1), MCP-1 (CCL2), MIP1-α (CCL3), MIP1-β (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-α and MIP1-β with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.

scholarly journals Restriction of HIV-1 Infection in Sickle Cell Trait

2021 ◽  
Author(s):  
Namita Kumari ◽  
Seyed Mehdi Nouraie ◽  
Asrar Ahmad ◽  
Hatajai Lassiter ◽  
Javed I Khan ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Mononuclear Cells ◽  
Sickle Cell Trait ◽  
Ex Vivo ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Living With Hiv ◽  
Hiv 1

Patients with Sickle cell disease (SCD) have lower risk for HIV-1 infection. We showed restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory and hemolytic factors including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs demonstrated ~2-fold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-Long Terminal Repeats (LTR) circles, HIV-1 integration and gag RNA expression. SCT PBMCs had higher HO-1 mRNA and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population level effect of SCT on HIV-1 prevalence, we assessed SCT trait among women living with HIV (WLH) in the Women Interagency HIV-1 Study (WIHS). Among WIHS African American participants, prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; OR 0.57; 95%CI = 0.36-0.92, p=0.020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow up (p=0.003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors including HO-1 and RNR2 might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.

scholarly journals Soluble Epoxide Hydrolase 2 Expression Is Elevated in Obese Humans and Decreased by Physical Activity

2020 ◽  
Vol 21 (6) ◽  
pp. 2056 ◽  
Author(s):  
Abdelkrim Khadir ◽  
Sina Kavalakatt ◽  
Dhanya Madhu ◽  
Preethi Cherian ◽  
Fahd Al-Mulla ◽  
...  
Keyword(s):  
Physical Activity ◽  
Er Stress ◽  
Epoxide Hydrolase ◽  
Mononuclear Cells ◽  
Metabolic Stress ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Activating Transcription Factor ◽  
Factor Α

Epoxide hydrolase 2 (EPHX2) is an emerging therapeutic target in several immunometabolic disorders. EPHX2 metabolizes anti-inflammatory epoxyeicosatrienoic acids into pro-inflammatory diols. The contribution of EPHX2 activity to human obesity remains unexplored. We compared the expression of EPHX2 between lean and obese humans (n = 20 each) in subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs) using RT-PCR, Western Blot analysis, immunohistochemistry, and confocal microscopy before and after a 3-month physical activity regimen. We also assessed EPHX2 levels during preadipocyte differentiation in humans and mice. EPHX2 mRNA and protein expression were significantly elevated in obese subjects, with concomitant elevated endoplasmic reticulum (ER) stress components (the 78-kDa glucose-regulated protein; GRP78, and the Activating transcription factor 6; ATF6) and inflammatory markers (Tumor necrosis factor-α; TNFα, and Interleukin 6; IL6) as compared to controls (p < 0.05). EPHX2 mRNA levels strongly correlated with adiposity markers. In obese individuals, physical activity attenuated EPHX2 expression levels in both the SAT and PBMCs, with a parallel decrease in ER stress and inflammation markers. EPHX2 expression was also elevated during differentiation of both human primary and 3T3-L1 mouse preadipocytes. Mediators of cellular stress (palmitate, homocysteine, and macrophage culture medium) also increased EPHX2 expression in 3T3-L1 preadipocytes. Our findings suggest that EPHX2 upregulation is linked to ER stress in adiposity and that physical activity may attenuate metabolic stress by reducing EPHX2 expression.

scholarly journals Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Lingxiao Xu ◽  
Qiuyue Peng ◽  
Wenhua Xuan ◽  
Xiaoke Feng ◽  
Xiangqing Kong ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
Synovial Fibroblasts ◽  
Cartilage Degradation ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
Peripheral Blood Mononuclear ◽  
Matrix Metalloproteinase 3 ◽  
Protein Levels ◽  
And Cartilage

We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation whenex vivoOA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

scholarly journals Steroid and Antihistamines Modulate Rantes Release in Cultured Peripheral Blood Mononuclear Cells of Atopic Patients

2002 ◽  
Vol 15 (1) ◽  
pp. 27-34 ◽  
Author(s):  
M. Di Gioacchino ◽  
N. Verna ◽  
E. Cavallucci ◽  
F. Paolini ◽  
R. Caruso ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Allergic Inflammation ◽  
Treated Group ◽  
Peripheral Blood Mononuclear ◽  
Diurnal Variability ◽  
Cell Recruitment ◽  
Blood Mononuclear Cells ◽  
Pre Treatment

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by mini-Wright. PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.

Hypersensitivity Immune Reaction as a Mechanism for Dilevalol-Associated Hepatitis

1992 ◽  
Vol 26 (7-8) ◽  
pp. 924-926 ◽  
Author(s):  
Vasco A.J. Maria ◽  
Rui M.M. Victorino
Keyword(s):  
Liver Injury ◽  
Healthy Subject ◽  
Proliferative Response ◽  
Mononuclear Cells ◽  
Immune Reaction ◽  
Ex Vivo ◽  
Peripheral Blood Mononuclear ◽  
Lymphocyte Sensitization ◽  
Before And After ◽  
Lymphocyte Reactivity

OBJECTIVE: To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol-induced liver injury. PATIENT: A 58-year-old woman with a clinical diagnosis of dilevalol-induced liver injury. METHODS: Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. RESULTS: No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. CONCLUSIONS: The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo-prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol-induced liver injury.

scholarly journals Possible role of a hydrogen peroxide-mediated mechanism in glucocorticoid receptor functional alterations associated with moderate asthma

2008 ◽  
Vol 60 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Tatjana Perisic ◽  
M. Sreckovic ◽  
Gordana Matic
Keyword(s):  
Hydrogen Peroxide ◽  
Glucocorticoid Receptor ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Pulmonary Inflammation ◽  
Peripheral Blood Mononuclear ◽  
Moderate Asthma ◽  
Asthmatic Patients ◽  
Healthy Donors ◽  
Induced Changes

It is well known that pathogenesis and maintenance of chronic asthma is associated with alterations of glucocorticoid receptor (GR) function, and also with persistent pulmonary inflammation, the important mediators of which are reactive oxygen and nitrogen species. In this paper, we tested a hypothesis that GR functional alterations in asthma result from the action of oxidants. To that end, we conducted a series of ex vivo treatments of peripheral blood mononuclear cells (PBMCs) of healthy donors with oxidizing agents (3 morpholinosydnonimine, SIN1; S-nitroso-N-acetyl-penicillamine, SNAP; and hydrogen peroxide, H2O2) and compared the resulting GR modifications with those previously noticed in asthmatic patients. The results show that treatment of PBMCs by H2O2 provoked an increase in the level of GR protein, accompanied by a rise in the number of hormone-binding sites and a decline in the receptor's affinity for the hormone. The H2O2 induced changes, including a characteristic GR isoprotein expression pattern, were found to be very similar to the GR changes previously observed in PBMCs of moderate asthmatic patients, but not in mild asthmatics and healthy subjects. Treatment with the other oxidants applied herein produced different effects or exerted no influence on GR. Thus, this study provides preliminary data suggesting that functional alterations of the GR associated with moderate asthma may be mediated by redox mechanisms that are based on oxidative and regulatory actions of H2O2.

Systemic modulatory effects of the treatment with IL-2 of lung metastasis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2560-2560
Author(s):  
D. Diaz ◽  
L. Chara ◽  
J. Chevarria ◽  
V. Navas ◽  
E. Esteban ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Renal Carcinoma ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Wilcoxon Test ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Induced Apoptosis

2560 Background: IL-2 is a drug that is employed in the treatment of several tumors due to its capacity of restore or increase the regulatory and effector function of the immune system. These effects have been demonstrated with the administration of the drug by intravenous and subcutaneous ways. Recently, it has been observed that the inhaled IL-2 administration is effective in the treatment of lung and renal cell carcinoma metastasis. However, it is unknown if this therapeutic effect is accompanied of systemic and local modulatory effects. Objectives: To compare spontaneous and mitogen-induced apoptosis in lymphocytes of renal carcinoma patients before and after treatment with inhaled IL-2. Methods: Peripheral blood mononuclear cells were purified from 7 patients with renal carcinoma before and after treatment with inhaled IL-2. The cells were characterized in a FACScalibur analyzer using fluorocrome-labeled monoclonal antibodies. The AI (or percentage of apoptotic cells, AI x 100) was calculated for T-cells expressing CD3, CD4, CD8, CD56, HLA-DR, CD25 and CD45RO/CD45RA antigens and NK-cells (CD3-CD56+ or CD3-CD16+). These AI were determined after 24 hours of culture under two conditions: without exogenous apoptosis inducers and in the presence of phytohemagglutinin. Comparisons between patients were carried out using the Wilcoxon test and were considered significant when p < 0.05. Results: A significant decrease in spontaneous ex vivo apoptosis was found in peripheral blood lymphocytes from renal carcinoma patients after treatment with inhaled IL-2 with respect to pretreatment values. This decrease occurred in T-cells and also in CD45RO expressing cells from both CD4+ and CD8+ subsets. A decrease of apoptosis was also observed in CD25+ expressing cells from CD3+, CD4+ and CD8+ subsets. A decrease in AI was found in mitogen induced apoptosis of CD25+ cells from CD3+, CD4+ and CD8+ subsets. Conclusions: The treatment with inhaled IL-2 has immunomodulatory effects that are observed at systemic level reducing the apoptosis of cells from several memory and activated T-cell subsets. No significant financial relationships to disclose.

scholarly journals Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Xiao ◽  
Meng Nie ◽  
Huanhuan Pang ◽  
Bohong Wang ◽  
Jieli Hu ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Fatal Outcome ◽  
Organ Injury ◽  
Cytokine Release ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear

AbstractCytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

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