scholarly journals TGR 5 signalling inhibits the production of pro‐inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease

Immunology ◽  
2013 ◽  
Vol 139 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Kazuaki Yoneno ◽  
Tadakazu Hisamatsu ◽  
Katsuyoshi Shimamura ◽  
Nobuhiko Kamada ◽  
Riko Ichikawa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Cytokines ◽  
Pro Inflammatory Cytokines

scholarly journals Effects of JAK1-Preferential Inhibitor Filgotinib on Circulating Biomarkers and Whole Blood Genes/Pathways of Patients With Moderately to Severely Active Crohn’s Disease

2021 ◽  
Author(s):  
Xavier Roblin ◽  
Adrian Serone ◽  
Oh Kyu Yoon ◽  
Luting Zhuo, ◽  
Ethan Grant ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Whole Blood ◽  
Janus Kinase ◽  
Oncostatin M ◽  
Circulating Biomarkers ◽  
Amyloid A ◽  
Pro Inflammatory Cytokines

Abstract Background Pro-inflammatory cytokines are dysregulated in Crohn’s disease (CD) and could serve as surrogate markers to improve diagnostic and therapeutic approaches, potentially addressing an unmet need. We profiled circulating biomarkers and whole blood transcriptional pathway activity to identify those associated with CD using data from the phase 2 FITZROY study with filgotinib, an oral preferential janus kinase-1 inhibitor. Methods Patients with serum and whole blood samples taken from the induction period were included. Serum cytokines were measured (ELISA), whole blood RNA sequenced, and stool samples taken to measure fecal calprotectin (FC). Spearman’s Rank correlations were assessed between biomarkers and baseline disease activity; post-treatment endoscopic improvement was measured by the Simplified Endoscopy Score for CD (SES-CD), FC and the Crohn’s Disease Activity Index. Effect of filgotinib on circulating biomarkers was also evaluated. Results Serum biomarkers (n = 168) and whole blood RNA sequencing (n = 104) were assessed. Moderate correlation between serum analytes with SES-CD and FC was noted; most highly correlated were acute phase proteins CRP (rho = 0.35 [SES-CD] and 0.47 [FC]), serum amyloid A (rho = 0.40 and 0.39, respectively) and pro-inflammatory cytokines interleukin (IL)-6 (rho = 0.31 and 0.30, respectively), IL-22 (rho = 0.36 and 0.35, respectively), and oncostatin M (rho = 0.35 and 0.33, respectively). Filgotinib treatment was associated with reduction of many candidate biomarkers, particularly in patients with treatment response. Early changes in IL-6 and IL-10 may be prognostic for endoscopic response. Conclusions Several circulating factors with potential as CD activity biomarkers were identified. Larger studies are necessary to investigate the best utility of these markers for CD.

scholarly journals Systemic Molecular Mediators of Inflammation Differentiate Between Crohn’s Disease and Ulcerative Colitis, Implicating Threshold Levels of IL-10 and Relative Ratios of Pro-inflammatory Cytokines in Therapy

2019 ◽  
Vol 14 (1) ◽  
pp. 118-129 ◽  
Author(s):  
Miranda G Kiernan ◽  
J Calvin Coffey ◽  
Shaheel M Sahebally ◽  
Paul Tibbitts ◽  
Emma M Lyons ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Cytokines ◽  
Healthy Controls ◽  
Mediators Of Inflammation ◽  
Faecal Diversion ◽  
Inflammatory Bowel ◽  
Circulating Fibrocytes ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Faecal diversion is associated with improvements in Crohn’s disease but not ulcerative colitis, indicating that differing mechanisms mediate the diseases. This study aimed to investigate levels of systemic mediators of inflammation, including fibrocytes and cytokines, [1] in patients with Crohn’s disease and ulcerative colitis preoperatively compared with healthy controls and [2] in patients with Crohn’s disease and ulcerative colitis prior to and following faecal diversion. Methods Blood samples were obtained from healthy individuals and patients with Crohn’s disease or ulcerative colitis. Levels of circulating fibrocytes were quantified using flow cytometric analysis and their potential relationship to risk factors of inflammatory bowel disease were determined. Levels of circulating cytokines involved in inflammation and fibrocyte recruitment and differentiation were investigated. Results Circulating fibrocytes were elevated in Crohn’s disease and ulcerative colitis patients when compared with healthy controls. Smoking, or a history of smoking, was associated with increases in circulating fibrocytes in Crohn’s disease, but not ulcerative colitis. Cytokines involved in fibrocyte recruitment were increased in Crohn’s disease patients, whereas patients with ulcerative colitis displayed increased levels of pro-inflammatory cytokines. Faecal diversion in Crohn’s disease patients resulted in decreased circulating fibrocytes, pro-inflammatory cytokines, and TGF-β1, and increased IL-10, whereas the inverse was observed in ulcerative colitis patients. Conclusions The clinical effect of faecal diversion in Crohn’s disease and ulcerative colitis may be explained by differing circulating fibrocyte and cytokine responses. Such differences aid in understanding the disease mechanisms and suggest a new therapeutic strategy for inflammatory bowel disease.

In vitro evaluation of IL-18 effects in Crohn's disease

2001 ◽  
Vol 120 (5) ◽  
pp. A316-A317
Author(s):  
P MAERTEN ◽  
S COLPAERT ◽  
Z LIU ◽  
K GEBOES ◽  
J CEUPPENS ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
In Vitro Evaluation

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

2020 ◽  
Vol 35 (3) ◽  
pp. 233-238
Author(s):  
Muflihatul Muniroh
Keyword(s):  
Inflammatory Cytokines ◽  
Health Concern ◽  
Brain Cells ◽  
Preventive Strategy ◽  
Hearing Impairments ◽  
Sensory Disturbances ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

Cladribine inhibits secretion of pro-inflammatory cytokines and phagocytosis in human monocyte-derived M1 macrophages in-vitro

2021 ◽  
Vol 91 ◽  
pp. 107270
Author(s):  
Caroline B.K. Mathiesen ◽  
Asha M. Rudjord-Levann ◽  
Monika Gad ◽  
Jesper Larsen ◽  
Finn Sellebjerg ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Human Monocyte ◽  
M1 Macrophages ◽  
Pro Inflammatory Cytokines

ACTIVATED INTESTINAL MUSCLE CELLS PROMOTE PREADIPOCYTE MIGRATION: A NOVEL MECHANISM OF CREEPING FAT FORMATION IN CROHN’S DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S34-S34
Author(s):  
Ren Mao ◽  
Genevieve Doyon ◽  
Ilyssa Gordon ◽  
Jiannan Li ◽  
Sinan Lin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Muscularis Propria ◽  
Dominant Factor ◽  
Stricture Formation ◽  
Intestinal Tissue ◽  
Mesenteric Fat

Abstract Background and Aims Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn’s disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. Methods Tissues from normal, ulcerative colitis, non-strictured and strictured Crohn’s disease intestinal specimens were obtained. Fresh and decellularized tissue, mesenteric fat explants, primary human adipocytes, pre-adipocytes, muscularis propria cells, and native extracellular matrix were used in multiple ex vivo and in vitro systems involving cell growth, differentiation and migration, proteomics, and integrin expression. Results Crohn’s disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by TGF-b1. The muscle cell-derived matrix triggered migration of pre-adipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the pre-adipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularized intestinal tissue extracellular matrix. Conclusion Crohn’s disease creeping fat appears to result from the migration of pre-adipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.

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