scholarly journals FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure

2021 ◽  
Vol 7 (29) ◽  
pp. eabf4335
Author(s):  
Alejandra González-Loyola ◽  
Esther Bovay ◽  
Jaeryung Kim ◽  
Tania Wyss Lozano ◽  
Amélie Sabine ◽  
...  
Keyword(s):  
Vascular Function ◽  
Multiorgan Failure ◽  
Lymphatic Endothelium ◽  
Commensal Microbiota ◽  
Peripheral Lymph ◽  
Cytokine Levels ◽  
Organ Specific ◽  
Inflammatory Bowel ◽  
Angiopoietin 2 ◽  
Circulating Levels

The mechanisms maintaining adult lymphatic vascular specialization throughout life and their role in coordinating inter-organ communication to sustain homeostasis remain elusive. We report that inactivation of the mechanosensitive transcription factor Foxc2 in adult lymphatic endothelium leads to a stepwise intestine-to-lung systemic failure. Foxc2 loss compromised the gut epithelial barrier, promoted dysbiosis and bacterial translocation to peripheral lymph nodes, and increased circulating levels of purine metabolites and angiopoietin-2. Commensal microbiota depletion dampened systemic pro-inflammatory cytokine levels, corrected intestinal lymphatic dysfunction, and improved survival. Foxc2 loss skewed the specialization of lymphatic endothelial subsets, leading to populations with mixed, pro-fibrotic identities and to emergence of lymph node–like endothelial cells. Our study uncovers a cross-talk between lymphatic vascular function and commensal microbiota, provides single-cell atlas of lymphatic endothelial subtypes, and reveals organ-specific and systemic effects of dysfunctional lymphatics. These effects potentially contribute to the pathogenesis of diseases, such as inflammatory bowel disease, cancer, or lymphedema.

scholarly journals Assessment of Growth Factors, Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2964
Author(s):  
Shankargouda Patil ◽  
Luca Testarelli
Keyword(s):  
Growth Factors ◽  
Trigeminal Neuralgia ◽  
Chemokine Receptors ◽  
Normal Subjects ◽  
Lower Growth ◽  
Inflammatory Microenvironment ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Cellular Markers ◽  
Angiopoietin 2

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1β, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN.

scholarly journals Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Julie Mondet ◽  
Kais Hussein ◽  
Pascal Mossuz
Keyword(s):  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Phenotypic Correlation ◽  
Hematopoietic Malignancies ◽  
Markers Of Inflammation ◽  
Functional Symptoms ◽  
Cytokine Levels ◽  
Clinical Interest ◽  
Circulating Levels

Cytokines are well known mediators of numerous physiological and pathological processes. They contribute to the regulation of normal hematopoiesis but increasing data suggest that they also have a clinical impact in some hematopoietic malignancies. In particular, there is evidence that cytokines are implicated in the functional symptoms of Philadelphia negative myeloproliferative neoplasms (Ph− MPNs), suggesting that evaluation of circulating levels of cytokines could be of clinical interest for the characterization of patients at the time of diagnosis and for disease prognosis. In this review, we present the current knowledge on alteration of circulating cytokine profiles in MPNs and their role in myelofibrosis pathogenesis. Phenotypic correlation, prognostic value of cytokines, and impact of JAK inhibitors are also discussed.

scholarly journals The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis

2021 ◽  
Author(s):  
Emma Haley ◽  
Mederbek Matmusaev ◽  
Imtiyaz N. Hossain ◽  
Sean Davin ◽  
Tammy M. Martin ◽  
...  
Keyword(s):  
Weight Loss ◽  
Genetic Background ◽  
Skin Inflammation ◽  
Control Mechanisms ◽  
Adult Mice ◽  
Severe Arthritis ◽  
Cytokine Levels ◽  
Clinical Arthritis ◽  
Organ Specific ◽  
The Impact

AbstractBackgroundOverexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated.MethodsWe compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA.FindingsMale B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight.ConclusionsSystemic IL-23 overexpression results in spondyloarthritis-like disease in B10.RIII mice. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests organ-specific genetic control mechanisms of IL-23 driven inflammation. Discrepancies regarding the phenotype of IL-23 induced disease in different labs and the sexual dimorphism observed in this study warrant further exploration.

scholarly journals Elevated antiviral, myeloid and endothelial inflammatory markers in severe COVID-19

2020 ◽  
Author(s):  
Ryan S Thwaites ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Matthew Siggins ◽  
Felicity Liew ◽  
Clark D Russell ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Endothelial Cell Activation ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Host Inflammatory Response

Introductory paragraphThe mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. The host inflammatory response contributes to lung injury, but circulating mediators levels fall below those in classical ‘cytokine storms’. We analyzed serial plasma samples from 619 patients hospitalized with COVID-19 recruited through the prospective multicenter ISARIC clinical characterization protocol U.K. study and 39 milder community cases not requiring hospitalization. Elevated levels of numerous mediators including angiopoietin-2, CXCL10, and GM-CSF were seen at recruitment in patients who later died. Markers of endothelial injury (angiopoietin-2 and von-Willebrand factor A2) were detected early in some patients, while inflammatory cytokines and markers of lung injury persisted for several weeks in fatal COVID-19 despite decreasing antiviral cytokine levels. Overall, markers of myeloid or endothelial cell activation were associated with severe, progressive, and fatal disease indicating a central role for innate immune activation and vascular inflammation in COVID-19.

scholarly journals Effect of Weight Loss Surgery on Biomarkers of Angiogenesis in Obese Patients

2020 ◽  
Vol 30 (9) ◽  
pp. 3417-3425 ◽  
Author(s):  
Maciej Wiewiora ◽  
Anna Mertas ◽  
Marek Gluck ◽  
Alicja Nowowiejska-Wiewiora ◽  
Zenon Czuba ◽  
...  
Keyword(s):  
Weight Loss ◽  
Growth Factor ◽  
Weight Loss Surgery ◽  
Significant Negative Correlation ◽  
Vascular Endothelial ◽  
Obese Patients ◽  
Platelet Endothelial Cell Adhesion ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Circulating Levels

Abstract Background The present study aims to clarify the effects of weight loss on biomarkers associated with angiogenesis in patients who underwent laparoscopic sleeve gastrectomy (SG) or adjustable gastric banding (LAGB) in the 12-month follow-up study. Materials and Methods We studied 24 obese patients who underwent laparoscopic weight loss surgery, 13 of whom underwent SG and 11 of whom underwent LAGB. We evaluated the circulating level of angiogenesis biomarkers preoperatively and 12 months after surgery. Results Before surgery, the following angiogenic circulating factors were significantly higher than those of healthy subjects: angiopoietin 2 (ANG-2) (p < .05), granulocyte colony-stimulating factor (G-CSF) (p < .05), hepatocyte growth factor (HGF) (p < .01), platelet endothelial cell adhesion molecule (PECAM-1) (p < .01), and vascular endothelial growth factor (VEGF) (p < .05). The following angiogenesis biomarkers decreased significantly after weight loss compared with their baseline values: ANG-2 (p < .05), follistatin (p < .05), HGF (p < .01), PECAM-1 (p < .01), and VEGF (p < .05). There were no significant differences in the circulating levels of angiogenesis biomarkers between individuals who underwent SG and those who underwent LAGB; however, HGF, PECAM-1, and VEGF tended to be lower after SG. %BMI correlated negatively with HGF, PECAM-1, and VEGF. A similar significant negative correlation was found for %WL and %EWL. WHR correlated with PDGF-B and VEGF. Conclusions We concluded that weight loss surgery induces the changes of circulating levels of angiogenesis biomarkers in obese patients. The changes in angiogenesis status in obese patients who lost weight after bariatric surgery depended on the amount of weight loss.

Angiogenin, angiopoietin-1, angiopoietin-2, and endostatin serum levels in inflammatory bowel disease

2011 ◽  
Vol 17 (4) ◽  
pp. 963-970 ◽  
Author(s):  
Konstantinos A. Oikonomou ◽  
Andreas N. Kapsoritakis ◽  
Anastasia I. Kapsoritaki ◽  
Anastassios C. Manolakis ◽  
Elisavet K. Tiaka ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Serum Levels ◽  
Inflammatory Bowel ◽  
Angiopoietin 2 ◽  
Angiopoietin 1

Autoimmune Disease (AD) in Patients with Myelodysplastic Syndrome (MDS): A Retrospective Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4736-4736
Author(s):  
Jeyanthi Ramanarayanan ◽  
Alan N. Baer ◽  
Minoo Battiwalla ◽  
Laurie A. Ford ◽  
Meir Wetzler ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Systemic Vasculitis ◽  
Multiorgan Failure ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Entire Cohort ◽  
Double Stranded Dna ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Autoimmune disease (AD) can manifest uncommonly either at the time of diagnosis of MDS or during its course. When present, AD generally responds to immunosuppressive therapies, but cytopenias and immunosuppression associated with MDS compromise delivery of these therapies. Few studies have investigated the impact of co-existing AD on the course and outcome of patients with MDS. Our objective was to evaluate the clinical manifestations, laboratory characteristics, response to therapy and survival of MDS patients with AD. Records of patients evaluated at Roswell Park Cancer Institute with pathologically demonstrated MDS between 1993 and 2003 (n=277) were reviewed and patients with evidence of AD were identified. Patients with laboratory abnormalities without disease manifestations were excluded, as were patients with therapy-related MDS following treatment for AD. 13 patients (4%) were identified with co-existing MDS and AD. The initial presentation was AD in 6 (46%) and MDS in 4 (31%), while 3 patients (23%) had near-simultaneous diagnoses of both conditions. The spectrum of AD in these patients included systemic vasculitis in 3 patients, systemic lupus erythematosus in two and rheumatoid arthritis, temporal arteritis, cryoglobulinemia, aphthous stomatitis, pyoderma gangrenosum, inflammatory bowel disease, erythema nodosum and Evans syndrome in one patient each. Anti-double stranded DNA (levels ≥ 40.0 u/ml; normal range 0.0–3.5u/ml), ANA (≥1:160), cold agglutinins, low C3 and elevated ESR (≥100mm/hr) were the serological abnormalities detected at the time of AD diagnosis. Eleven of 13 patients were female, and median age at diagnosis of MDS was 65 years, while the entire cohort was 44% female (p=0.005) and had a median age of 71 yrs at diagnosis. FAB subtypes were RA (n=7), RAEB (n=3), CMMoL (n=2) and RARS (n=1). Cytogenetics were normal in 5 patients; abnormalities in the other 8 patients included −7, +8, and del(5q). The median survival of patients from diagnosis of MDS was 48 months and the survival from diagnosis of AD was 46 months. Known causes of death in 6 patients included sepsis, intracranial hemorrhage, lung cancer and transplant-associated multiorgan failure. Based on this study, AD occurs in 4% of MDS patients, predominantly affects female patients, and has heterogeneous clinical manifestations.The pathobiologic implication of the occurrence of AD at the same time or after the diagnosis of MDS is that the dysplastic clone might be responsible for the induction of immune dysregulation.

Elevated Circulating Levels of Thrombospondin-1 in Plasma Are Associated with Increased Circulating Levels of TGFb and Pro-Inflammatory Cytokines in Patients Afflicted with Rheumatoid Arthritis: Utilization of the Multiplexed Protein Profiling on Microarray by Rolling-Circle Amplification Technique.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1284-1284
Author(s):  
Mario C. Rico ◽  
Joanne M. Manns ◽  
Hien Nguyen ◽  
Nicole Beharry ◽  
Meera Reddy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Rolling Circle Amplification ◽  
Protein Profiling ◽  
Rolling Circle ◽  
Cytokine Levels ◽  
Thrombospondin 1 ◽  
Circulating Levels ◽  
Pro Inflammatory Cytokines

Abstract Rheumatoid Arthritis (RA) is a chronic, autoimmune disease that affects a vast population worldwide with women being afflicted three times more than men. There is evidence for an increased risk of cardiovascular events in RA patients compared to the general population. These cardiovascular events may be associated with the chronic inflammatory state in which activation of coagulation leads to thrombin generation. Our laboratory has evidence that thrombospondin-1 (TSP1), an adhesive molecule that plays a major role in RA, promotes thrombin generation on the surface of a monocytic cell line (Isordia-Salas et al, Thromb Res.2005;116(6)). We also have documented that disrupting the TSP1 interaction on human neutrophils prevents the development of erosive arthritis in an experimental animal model (Manns et al, Arthritis and Rheumatism54(8), 2006). This observation is mediated by a novel pathway whereby TSP1 induces the up-regulation of Connective Tissue Growth Factor (CTGF). Therefore, to assess whether our in vitro and in vivo observations can be extrapolated to human disease, blood samples were collected from 20 patients afflicted with rheumatoid arthritis and 13 from healthy donors which served as the negative control. Plasma samples were separated and analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) to determine the levels of transforming growth factor beta (TGF-β), protrombin F1+2 fragments (F1+2) and thrombospondin-1, and by multiplexed cytokine protein profiling on microarray by rolling-circle amplification (RCA) to determine cytokine levels. The F1+2 plasma levels showed an elevated trend in the RA group (p=0.06). TSP1 plasma levels were significantly increased in the RA group compared to the normal control (p=0.0004). Pro-inflammatory cytokine levels including IL-1β (p=0.0365), IL-6 (p=0.0029), TNF-α (p=0.0339), interferon-inducible protein 10 (p=0.0003) and macrophage inflammatory protein -1α (p=0.0012) were found elevated in the RA group compared to the normal control group. Some regulatory cytokines such as transforming growth factor-β (0.06), interferon-gamma (p=0.06) and IL-13 (p=0.22) showed no statistically significance between groups, but all of them showed a trend for higher circulation levels in plasma in the RA group. In summary, comparison between normal individuals and RA patients showed an increase in the levels of cytokines in the RA afflicted patients confirming what has been reported in the literature. We were able to correlate an increase in proteolytic factors and TSP1 levels in the RA patients with an increase of pro-inflammatory cytokines. Further studies are needed to elucidate why TSP1 acts as a pro-inflammatory molecule on the neutrophil surface of the RA patients.

scholarly journals Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon

2017 ◽  
Vol 131 (21) ◽  
pp. 2611-2626 ◽  
Author(s):  
Daniel G. Couch ◽  
Chris Tasker ◽  
Elena Theophilidou ◽  
Jonathan N. Lund ◽  
Saoirse E. O’Sullivan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Human Colon ◽  
Interferon Γ ◽  
Cytokine Levels ◽  
Drug Treatments ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Trpv1 Antagonist ◽  
Factor Α

Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.

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