Are mononuclear cells the site of action of steroids & “anti-inflammatory” cytokines in colitis?

1998 ◽  
Vol 114 ◽  
pp. A1022
Author(s):  
JD Linehan ◽  
DA Robertson ◽  
J Westwick
Keyword(s):  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Site Of Action ◽  
Anti Inflammatory

scholarly journals Intrauterine Growth Restriction: Cytokine Profiles of Trophoblast Antigen-Stimulated Maternal Lymphocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Raj Raghupathy ◽  
Majedah Al-Azemi ◽  
Fawaz Azizieh
Keyword(s):  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Intrauterine Growth Restriction ◽  
Mononuclear Cells ◽  
Normal Pregnancy ◽  
Placental Insufficiency ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Anti Inflammatory ◽  
Ifnγ And Tnfα

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR.

Pathogenetic molecular mechanisms of chronic rhinosinusitis with nasal polyps associated with asthma

2021 ◽  
Vol 31 (1) ◽  
pp. 7-19
Author(s):  
O. M. Kurbacheva ◽  
M. E. Dyneva ◽  
I. P. Shilovskiy ◽  
E. L. Savlevich ◽  
V. I. Kovchina ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Inflammatory Cytokines ◽  
Nasal Polyps ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Clinical Laboratory ◽  
Compensatory Mechanism ◽  
Local Immunity ◽  
Polyp Tissue ◽  
Anti Inflammatory

The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1st was healthy control (Normal); the 2nd had allergic BA associated with CRSwNP; the 3rd had nonallergic BA associated with CRSwNP; the 4th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.

scholarly journals Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Phurpa Wangchuk ◽  
Catherine Shepherd ◽  
Constantin Constantinoiu ◽  
Rachael Y. M. Ryan ◽  
Konstantinos A. Kouremenos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Clinical Signs ◽  
Gas Chromatography Mass Spectrometry ◽  
Trinitrobenzenesulfonic Acid ◽  
Human Leukocytes ◽  
Polar Metabolites ◽  
Anti Inflammatory

ABSTRACT Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Using a murine model of trinitrobenzenesulfonic acid-induced colitis and human peripheral blood mononuclear cells, we demonstrated that low-molecular-weight metabolites derived from both somatic extracts (LMWM-SE) and excretory-secretory products (LMWM-ESP) of the hookworm, Ancylostoma caninum, display anti-inflammatory properties. Administration to mice of LMWM-ESP as well as sequentially extracted fractions of LMWM-SE using both methanol (SE-MeOH) and hexane-dichloromethane-acetonitrile (SE-HDA) resulted in significant protection against T cell-mediated immunopathology, clinical signs of colitis, and impaired histological colon architecture. To assess bioactivity in human cells, we stimulated primary human leukocytes with lipopolysaccharide in the presence of hookworm extracts and showed that SE-HDA suppressed ex vivo production of inflammatory cytokines. Gas chromatography-mass spectrometry (MS) and liquid chromatography-MS analyses revealed the presence of 46 polar metabolites, 22 fatty acids, and five short-chain fatty acids (SCFAs) in the LMWM-SE fraction and 29 polar metabolites, 13 fatty acids, and six SCFAs in the LMWM-ESP fraction. Several of these small metabolites, notably the SCFAs, have been previously reported to have anti-inflammatory properties in various disease settings, including IBD. This is the first report showing that hookworms secrete small molecules with both ex vivo and in vivo anti-inflammatory bioactivity, and this warrants further exploration as a novel approach to the development of anti-inflammatory drugs inspired by coevolution of gut-dwelling hookworms with their vertebrate hosts.

scholarly journals Induction of Pro- and Anti-Inflammatory Cytokines by Borrelia burgdorferi Lipoproteins in Monocytes Is Mediated by CD14

1999 ◽  
Vol 67 (1) ◽  
pp. 140-147 ◽  
Author(s):  
Guillermo H. Giambartolomei ◽  
Vida A. Dennis ◽  
Barbara L. Lasater ◽  
Mario T. Philipp
Keyword(s):  
Borrelia Burgdorferi ◽  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Human Peripheral Blood ◽  
Peptide Sequence ◽  
Monocytic Cell ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

ABSTRACT We previously showed that heat-killed Borrelia burgdorferi spirochetes and lipidated outer surface protein A (L-OspA) stimulated the in vitro production of interleukin-10 (IL-10) in peripheral blood mononuclear cells (PBMC) from uninfected humans and rhesus monkeys (G. Giambartolomei et al., Infect. Immun. 66:2691–2697, 1998). Here we demonstrate that uninfected human peripheral blood monocytes, but not B or T cells, are the cells that transcribe the IL-10 cytokine gene in response to heat-killed B. burgdorferi. B. burgdorferi similarly induced an upregulation of the IL-1β and IL-6 cytokine genes in monocytes and the production of IL-10 and IL-6 in culture supernatants of the human monocytic cell line THP-1. Purified L-OspA (but not unlipidated OspA [U-OspA] or U-OspC) also stimulated the production of both cytokines in THP-1 cells in a dose-dependent fashion, suggesting that acylation of the OspA protein molecule is required for the production of both anti- and pro-inflammatory cytokines in naive monocytes. A lipohexapeptide that contained the tripalmitoyl-modified cysteine motif (Pam3Cys-Hex) of B. burgdorferi lipoproteins but with an arbitrary peptide sequence had the same effect. Monoclonal antibodies (MAbs) MY4 and 60bca, both of which bind to CD14 and are known to block lipopolysaccharide (LPS)-mediated cytokine production, were able to block L-OspA-mediated IL-10 and IL-6 cytokine production. In contrast, MAb 26ic, which also binds to CD14 but does not block LPS function, failed to inhibit L-OspA-mediated cytokine production. These data suggest that activation of monocytes and production of both anti- and pro-inflammatory cytokines induced by lipoproteins proceeds via the CD14 receptor. LPS binding protein was not required for OspA-induced cytokine production. Our results demonstrate that pro- and anti-inflammatory cytokines induced by B. burgdorferilipoproteins in PBMC are produced by monocytes and that lipoprotein and LPS signaling pathways share at least the initial signaling event that involves the CD14 receptor.

scholarly journals Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4322
Author(s):  
Sergio Ramírez-Pérez ◽  
Luis Alexis Hernández-Palma ◽  
Edith Oregon-Romero ◽  
Brian Uriel Anaya-Macías ◽  
Samuel García-Arellano ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Primary Response ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Cytokine Production ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pathway Inhibition

The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.

scholarly journals Hookworm-derived small molecule extracts suppress pathology in a mouse model of colitis and inhibit secretion of key inflammatory cytokines in primary human leukocytes

2018 ◽  
Author(s):  
Phurpa Wangchuk ◽  
Constantin Constantinoiu ◽  
Konstantinos A. Kouremenos ◽  
Luke Becker ◽  
Linda Jones ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Mononuclear Cells ◽  
Somatic Tissue ◽  
Gas Chromatography Mass Spectrometry ◽  
Human Leukocytes ◽  
Tissue Extracts ◽  
Chromatography Mass Spectrometry ◽  
Anti Inflammatory

ABSTRACTIatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Here we use a metabolomics approach to characterize the non-protein small molecule complement of hookworms. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses of somatic tissue extracts revealed the presence of 52 polar metabolites and 22 non-polar components including short chain fatty acids (SCFA). Several of these small metabolites, notably the SCFA, have been shown to have anti-inflammatory properties in various diseases, including IBD. Using a murine model of colitis and human peripheral blood mononuclear cells, we demonstrate that somatic tissue extracts of the hookworm Ancylostoma caninum contain small molecules with anti-inflammatory activities. Of the five extracts tested, two of them significantly protected mice against T cell-mediated immunopathology and weight loss in a chemically-induced colitis model. Moreover, one of the anti-colitic extracts suppressed ex vivo production of inflammatory cytokines from primary human leukocytes. While the origin of the SCFA (parasite or host microbiota-derived) present in the hookworm somatic tissue extracts cannot be ascertained from this study, it is possible that A. caninum may be actively promoting an anti-inflammatory host microbiome by facilitating immune crosstalk through SCFA production.

scholarly journals Neutrophil extracellular trap clearance by synovial macrophages in gout

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ji Hye Jeong ◽  
Su Jin Choi ◽  
Soo Min Ahn ◽  
Ji Seon Oh ◽  
Yong-Gil Kim ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Immunological Response ◽  
Neutrophil Extracellular Trap ◽  
Extracellular Traps ◽  
Sytox Green ◽  
Anti Inflammatory ◽  
Msu Crystals

Abstract Background Monosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs). We investigated whether synovial macrophages could clear NETs as a self-resolution mechanism in acute gouty arthritis. Methods Synovial fluid mononuclear cells (SFMCs) were incubated with NETs induced by MSU crystals. NET engulfment was determined based on neutrophil elastase (NE), myeloperoxidase (MPO), and SYTOX Green signals within synovial fluid CD14+ cells. In addition, the correlations between CD14+ cells, MPO-dsDNA complexes, and expression of pro- and anti-inflammatory cytokines were analyzed in the synovial fluid CD14+ macrophages of patients with gouty arthritis. Results Synovial fluid CD14+ macrophages significantly engulfed the MSU crystal-induced NETs, as evidenced by the alteration in SYTOX Green intensity or the presence of NE and MPO in the cytoplasm of CD14+ cells. The proportion of CD14+ macrophages was significantly and inversely correlated with levels of MPO-dsDNA complex in the synovial fluid of gout patients. Synovial fluid CD14+ macrophages cultured with NETs did not show a significant induction in pro- and anti-inflammatory cytokines. Conclusion Synovial fluid macrophages may play an important role in the resolution of MSU crystal-induced gouty inflammation by clearing NETs without causing any significant immunological response.

scholarly journals Weaning causes a prolonged but transient change in immune gene expression in the intestine of piglets

2021 ◽  
Author(s):  
Nienke de Groot ◽  
Fernando Fariñas ◽  
Carolina G Cabrera-Gómez ◽  
Francisco J Pallares ◽  
Guillermo Ramis
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Cytokine Gene Expression ◽  
Future Research ◽  
Immune Gene ◽  
Peripheral Blood Mononuclear ◽  
Gut Inflammation ◽  
Anti Inflammatory

Abstract Controlling gut inflammation is important in managing gut disorders in the piglet after weaning. Establishing patterns of inflammation markers in the time subsequent to weaning is important for future research to determine if interventions are effective in controlling gut inflammation. The objective of this study was to evaluate the intestinal inflammatory response during the post-weaning period in piglets. A 45-day study included 108 piglets (weaned at 22 days (d), body weight 5.53 ± 1.19 kg), distributed in 12 pens with nine pigs per pen. Histomorphometry, gene expression of pro- and anti-inflammatory cytokines and the quantity of Immunoglobulin (Ig) A producing cells were measured in jejunum, ileum and colon on days 0, 15, 30 and 45 post-weaning. Cytokine gene expression in peripheral blood mononuclear cells (PBMC) and Ig quantities were analysed in blood from piglets on day 0, 15, 30 and 45 post-weaning. Histomorphometrical results showed a lower villus length directly after weaning. Results demonstrated a post-weaning intestinal inflammation response for at least 15 days post-weaning by upregulation of IgA producing cells and IFN-γ, IL-1α, IL-8, IL-10, IL-12α and TGF-β in jejunum, ileum and colon. IgM and IgA was upregulated at day 30 post-weaning. IgG was downregulated at day 15 post-weaning. The results indicate that weaning in piglets is associated with a prolonged and transient response in gene expression of pro- and anti-inflammatory cytokines and IgA producing cells in the intestine.

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