scholarly journals Distinct inflammatory gene expression in extraocular muscle and fat from patients with Graves’ orbitopathy

2017 ◽  
Vol 176 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Ivana Lopes Romero-Kusabara ◽  
José Vital Filho ◽  
Nilza Maria Scalissi ◽  
Keli Cardoso Melo ◽  
Giovanni Demartino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extraocular Muscle ◽  
Eye Disease ◽  
Mrna Levels ◽  
Inflammatory Gene Expression ◽  
Graves Orbitopathy ◽  
A Prospective Study ◽  
Design And Methods ◽  
Prospective Study Design ◽  
Normal Controls

Objective This study sought to compare patients with thyroid eye disease (TED) and normal controls with respect to the expression of the NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1 genes in orbital fat (OF) and extraocular muscle (EOM). Design and methods A prospective study design was used to evaluate 34 TED patients and 38 healthy controls. OF was harvested from 33 TED patients and 27 controls. EOM biopsies were obtained from 32 TED patients and 18 controls. Samples were examined by real-time PCR and evaluated using appropriate statistical analyses with a significance cut-off of P < 0.05. Results NR3C1 mRNA levels were higher in TED EOM (median 213 (96–376)) than those in control EOM (78 (34–138)) (P < 0.001), and NFKB expression was elevated in TED muscle (223 (31–520)) relative to that in control muscle (8 (6–31)) (P < 0.001). HSD11B1 expression was higher in TED EOM (0.78 (0.47–2.01)) than that in control EOM (0.22 (0.09–0.51)) (P < 0.001). Levels of CHUK, IKBKB, and FOS were higher in TED EOM (115 (20–223), 111 (54–299) and 0.11 (0.03–0.19), respectively) than those in control EOM (5.8 (2–13), 21 (5–52) and 0.05 (0.001–0.03) respectively) (P < 0.001). Conclusion Tissues involved in GO exhibited different mRNA levels of NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1. Gene expression in OF was similar for TED patients and controls. CHUK, IKBKB, FOS, NFKB, and HSD11B1 mRNA levels were higher in TED EOM than those in control EOM. NFKB was disproportionally elevated compared with NR3C1; this finding was indicative of a local proinflammatory profile.

scholarly journals Comparison of leptin gene expression in different adipose tissues in children and adults

2004 ◽  
pp. 579-584 ◽  
Author(s):  
E Schoof ◽  
A Stuppy ◽  
F Harig ◽  
R Carbon ◽  
T Horbach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Subcutaneous Tissue ◽  
Mrna Levels ◽  
Adipose Tissues ◽  
Metabolic Properties ◽  
Tissue Specimens ◽  
Plasma Leptin ◽  
Design And Methods

OBJECTIVE: Adipose tissue displays depot-specific metabolic properties and a predominant gene expression of leptin in subcutaneous tissue. The aim of the study was to evaluate leptin mRNA expression in various adipose tissues and to relate it to plasma leptin concentrations. Furthermore, developmental changes in leptin gene expression from childhood to adulthood were examined. DESIGN AND METHODS: Thoracic subcutaneous and intrathoracic adipose tissue specimens were obtained in 22 adults (51-81 years) and 23 children (0.1-17 years) undergoing cardiac surgery, and abdominal subcutaneous, omental and mesenterial fat specimens were collected from 21 adults (38-79 years) and 22 children (0.2-17 years) before abdominal surgery. Preoperative plasma leptin concentrations were measured by RIA. Leptin mRNA expression was quantified by TaqMan real-time PCR. RESULTS: In adults, there was no difference between leptin gene expression in subcutaneous and intrathoracic fat, whereas in children leptin mRNA expression was significantly higher in subcutaneous adipose tissue. In omental fat, leptin mRNA levels were significantly lower compared with subcutaneous and mesenterial sites in both children and adults. Adults revealed a significantly higher leptin gene expression in subcutaneous, omental and mesenterial adipose tissues than children. Subcutaneous and omental leptin gene expression are independent factors for plasma leptin concentrations in children and adults. CONCLUSION: Leptin is differentially expressed at different adipose tissue sites, a situation which is even more pronounced in children. There is a developmental increase in leptin mRNA expression in adipose tissue during childhood, reaching maximal capacity in adulthood.

scholarly journals A Case of Thyroid Eye Disease Revealed During Secondary Adrenal Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A910-A910
Author(s):  
Amira Ibrahim ◽  
Victoria Loseva
Keyword(s):  
Adrenal Insufficiency ◽  
Extraocular Muscle ◽  
Early Recognition ◽  
Thyroid Eye Disease ◽  
Eye Disease ◽  
Secondary Adrenal Insufficiency ◽  
Movement Restriction ◽  
Free T4 ◽  
Muscle Movement ◽  
Graves Orbitopathy

Abstract Introduction: Thyroid eye disease (TED) or Graves’ orbitopathy (GO) is an autoimmune disease of the retro-orbital tissues. GO is mostly associated with hyperthyroidism in 90% of patients; however, it may coexist with hypothyroid conditions in 5% of cases. Clinical Case: A 56-year-old male with a past medical history of autoimmune diseases including hypothyroidism and Ulcerative Colitis on chronic steroid therapy presented to the emergency department with nausea, fatigue, weight loss, and muscle weakness. The patient stated that his glucocorticoids were abruptly discontinued a month prior to his current presentation. On examination, vitals were stable. The patient was somnolent with a depressed mood. He had bilateral periorbital edema and bilateral eyeball protrusion, left more pronounced than right. Extraocular muscle movement revealed a delay in the lateral movement of the left eye causing double vision on exam. He had no starring look or lid lag. The thyroid gland was normal in size and contour. Initial Laboratories revealed a white blood cell count of 6.7 K/mcL (4-10 K/mcL) with 18% eosinophil count (0-5%). Cortisol at 8 AM was 2.9 mcg/dL (4.3 -22.4 mcg/dl). The patient was managed for secondary adrenal insufficiency and restarted immediately on Prednisone. A review of a recent CT scan of the head revealed bilateral proptosis with no signs of compressing lesions. Further thyroid studies revealed TSH of 2.9 mcIU/mL (0.3-3.7 mcIU/mL), free T4 of 0.8 ng/dL (0.75-2.0 ng/dL), free T3 of 1.6 ng/dL (2.4-4.2 ng/dL), TPO antibodies &lt;0.3 IU/mL (0.0-9.0 IU/mL) and TSH receptor antibodies 0.90 IU/L (reference range &lt;1.75 IU/L). The patient was then diagnosed with Hypothyroid Grave’s ophthalmopathy with negative antibodies given the evidence of proptosis on CT and exam revealing extraocular muscle movement restriction causing diplopia. The patient had a unique presentation of TED with hypothyroidism and asymmetric ophthalmic signs that were only manifested after the patient discontinued the prednisone and therefore unmasking the underlying disorder. Fortunately, in June of 2020, the US Food and Drug Administration (FDA) approved Teprotumumab (an insulin-like growth factor 1 [IGF-1] receptor inhibitor) for the treatment of Graves’ orbitopathy based on the findings from two 24-week trials comparing teprotumumab with placebo in 171 patients with active, moderate-to-severe orbitopathy. (1) Our patient was started on Levothyroxine along with Prednisone and referred for ophthalmology evaluation for possible qualification for Teprotumumab treatment. Conclusion: Clinician awareness of the unusual presentations of TED would allow for early recognition and prevention of progression, especially with the recently approved treatment modality. References: (1) Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ Et al. N Engl J Med. 2017;376(18):1748.

Dysregulation of BMPR2, Arginase II and HMGA2 Expression in Idiopathic Myelofibrosis and Secondary Myelofibrosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 792-792 ◽  
Author(s):  
Enli Liu ◽  
Adaani E. Frost ◽  
Uday R. Popat ◽  
Josef T. Prchal
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Mononuclear Cells ◽  
P Value ◽  
Mrna Levels ◽  
Idiopathic Myelofibrosis ◽  
Myeloid Metaplasia ◽  
Significant Difference ◽  
Arginase Ii ◽  
Normal Controls

Abstract Idiopathic myelofibrosis (IMF) is a fatal clonal myeloproliferative disorder, characterized by variable pancytopenia, splenomegaly, leukoerythroblastic blood smear, marrow fibrosis (MF), and myeloid metaplasia. Like all myeloproliferative disorders, it is due to an acquired somatic mutation of a single hematopoietic progenitor. MF has also been reported in systemic lupus and metastatic malignancies involving bone marrow. We have recently demonstrated the occurrence of MF in 85% patients with pulmonary hypertension (PH), which (unlike IMF) is associated with polyclonal hematopoiesis and normal number of circulating CD34+ cells. The pathophysiological mechanisms resulting in IMF and secondary MF (SMF) in PH remain still unclear. To date, 52 heterozygous germline mutations in the gene (BMPR2) encoding the bone morphogenetic protein type II receptor (BMPR-II) have been found to characterize many cases of familial (Lane, 2000) and sporadic primary PH (PPH) (Thomson, 2000). Recently, increased activity of arginase in pulmonary tissue of patients with PH was found. This may contribute to the pathogenesis of pulmonary hypertension by decreasing the substrate for NO synthesis. We examined BMPR2 and Arginase II mRNA levels by quantitative real-time RT-PCR in mononuclear cells (MNC), platelets (PLT) and granulocytes (GNC) from IMF patients and PH patients with secondary MF. We show for the first time that the mRNA level of BMPR2 is increased in PLT and GNC of IMF compared with normal controls. Arginase II mRNA was significantly increased in GNC of IMF as well as PH patients with SMF. Rearrangement and over expression of high-mobility group AT-hook2 (HMGA2) gene in myeloid progenitors in two patients with IMF was recently reported. This gene is known to play a major role in fetal growth and development, and is expressed in trace amount in adult lung, kidney, and synovia. We found significantly increased HMGA2 mRNA expression in MNC of IMF patients. In summary, the biomarkers studied here can be abnormal in both IMF and PH with secondary MF and may not be useful to discriminate between the two types of MF. Dysregulation of BMPR2, Arginase II and HMGA2 expression may play a pathophysiological role in MF of both IMF and PH. Expression of BMPR2 , Arginase II and HMGA2 in Blood Cells of IMF and SMF Gene Cells Control (ΔCT) Idiopathic MF (ΔCT) Secondary MF (ΔCT) *The P value represents a significant difference of gene expression in IMF or SMF compared with normal controls. A lower ΔCT indicates a higher gene expression. BMPR2 PLT 18.5±1.2 16.7±1.4 (p=0.038) * 18.4±2.2 (p=0.881) GNC 19.2±1.0 18.3±1.3 (p=0.009) * 19.1±1.2 (p=0.893) MNC 18.3±1.2 19.2±1.8 (p=0.059) 19.0±2.7 (p=0.554) Arginase II GNC 24.5±0.6 21.9±1.7 (p=0.000) * 22.6±1.2 (p=0.004) * MNC 24.4±3.5 24.4±3.9 (p=0.965) 22.5±2.4 (p=0.222) HMGA2 MNC 32.4±1.6 29.3±1.7 (p=0.000) * 30.8±1.8 (p=0.085)

scholarly journals Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1

2018 ◽  
Vol 9 ◽  
Author(s):  
Karima Kessal ◽  
Hong Liang ◽  
Ghislaine Rabut ◽  
Philippe Daull ◽  
Jean-Sébastien Garrigue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Dry Eye ◽  
Expression Profiling ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes

2005 ◽  
Vol 289 (2) ◽  
pp. G267-G273 ◽  
Author(s):  
Pu Qin ◽  
Lisa A. Borges-Marcucci ◽  
Mark J. Evans ◽  
Douglas C. Harnish
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Human Hepatocytes ◽  
Mrna Levels ◽  
Response Element ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Selective Agonist ◽  
Tnf Α ◽  
Dose Dependent

Previous studies have demonstrated a dramatic induction of inflammatory gene expression in livers from mice fed a high-fat, high-cholesterol diet containing cholate after 3–5 wk. To determine the contribution of cholate in mediating these inductions, C57BL/6 mice were fed a chow diet supplemented with increasing concentrations of cholic acid (CA) for 5 days. A dose-dependent induction in the hepatic levels of TNF-α, VCAM-1, ICAM-1, and SAA-2 mRNA were observed. As positive controls, a dose-dependent repression of cholesterol 7α-hydroxylase and a dose-dependent induction of small heterodimer partner (SHP) expression were also observed, suggesting that farnesoid X receptor (FXR) was activated. In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist. The involvement of FXR in CA-induced inflammatory gene expression was further investigated in the human hepatic cell line HepG2. Both ICAM-1 and SHP expression were induced in a dose- and time- dependent manner by treatment with the FXR-selective agonist GW4064. Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. Finally, the activity of FXR was mapped to a retinoic acid response element (RARE) site containing an imbedded farnesoid X response element (FXRE) on the human ICAM-1 promoter and FXR and retinoid X receptor were demonstrated to bind to this site. Finally, FXR-mediated activation of ICAM-1 could be further enhanced by TNF-α cotreatment in hepatocytes, suggesting a potential cooperation between cytokine and bile acid-signaling pathways during hepatic inflammatory events.

scholarly journals Astragaloside IV Inhibits NF-κB Activation and Inflammatory Gene Expression in LPS-Treated Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jian Zhang ◽  
Balz Frei
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cellular Adhesion ◽  
Mrna Levels ◽  
Astragaloside Iv ◽  
Chinese Medicinal Herb ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

In this study we investigated the role of astragaloside IV (AS-IV), one of the major active constituents purified from the Chinese medicinal herbAstragalus membranaceus, in LPS-induced acute inflammatory responses in micein vivoand examined possible underlying mechanisms. Mice were assigned to four groups: vehicle-treated control animals; AS-IV-treated animals (10 mg/kg b.w. AS-IV daily i.p. injection for 6 days); LPS-treated animals; and AS-IV plus LPS-treated animals. We found that AS-IV treatment significantly inhibited LPS-induced increases in serum levels of MCP-1 and TNF by 82% and 49%, respectively. AS-IV also inhibited LPS-induced upregulation of inflammatory gene expression in different organs. Lung mRNA levels of cellular adhesion molecules, MCP-1, TNFα, IL-6, and TLR4 were significantly attenuated, and lung neutrophil infiltration and activation were strongly inhibited, as reflected by decreased myeloperoxidase content, when the mice were pretreated with AS-IV. Similar results were observed in heart, aorta, kidney, and liver. Furthermore, AS-IV significantly suppressed LPS-induced NF-κB and AP-1 DNA-binding activities in lung and heart. In conclusion, our data provide newin vivoevidence that AS-IV effectively inhibits LPS-induced acute inflammatory responses by modulating NF-κB and AP-1 signaling pathways. Our results suggest that AS-IV may be useful for the prevention or treatment of inflammatory diseases.

Mice derived from in vitro αMEM-cultured preimplantation embryos exhibit postprandial hyperglycemia and higher inflammatory gene expression in peripheral leukocytes

2021 ◽  
Vol 85 (5) ◽  
pp. 1215-1226
Author(s):  
Shiori Ishiyama ◽  
Mayu Kimura ◽  
Nodoka Umihira ◽  
Sachi Matsumoto ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Postprandial Hyperglycemia ◽  
Postprandial Blood Glucose ◽  
Mrna Levels ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Peripheral Leukocytes ◽  
The Impact ◽  
Rice Diet

ABSTRACT We examined whether peripheral leukocytes of mice derived from in vitro αMEM-cultured embryos and exhibiting type 2 diabetes had higher expression of inflammatory-related genes associated with the development of atherosclerosis. Also, we examined the impact of a barley diet on inflammatory gene expression. Adult mice were produced by embryo transfer, after culturing two-cell embryos for 48 h in either α minimal essential media (α-MEM) or potassium simplex optimized medium control media. Mice were fed either a barley or rice diet for 10 weeks. Postprandial blood glucose and mRNA levels of several inflammatory genes, including Tnfa and Nox2, in blood leukocytes were significantly higher in MEM mice fed a rice diet compared with control mice. Barley intake reduced expression of S100a8 and Nox2. In summary, MEM mice exhibited postprandial hyperglycemia and peripheral leukocytes with higher expression of genes related to the development of atherosclerosis, and barley intake reduced some gene expression.

scholarly journals The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

2001 ◽  
pp. 529-534 ◽  
Author(s):  
A Lopez-Calderon ◽  
I Ibanez de Caceres ◽  
L Soto ◽  
T Priego ◽  
AI Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight Gain ◽  
Chronic Arthritis ◽  
Mrna Levels ◽  
Gh Receptor ◽  
Igf I ◽  
Male Wistar Rats ◽  
Design And Methods ◽  
I Gene ◽  
Gh Resistance

OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS- than in saline-treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.

scholarly journals HDAC3 Regulates Gingival Fibroblast Inflammatory Responses in Periodontitis

2019 ◽  
Vol 99 (1) ◽  
pp. 98-106 ◽  
Author(s):  
K.B. Lagosz ◽  
A. Bysiek ◽  
J.M. Macina ◽  
G.P. Bereta ◽  
M. Kantorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Mediators ◽  
Histone Deacetylases ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Gingival Fibroblast ◽  
Mrna Levels ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Inflammatory Activation

Histone deacetylases (HDACs) are important regulators of gene expression that are aberrantly regulated in several inflammatory and infectious diseases. HDAC inhibitors (HDACi) suppress inflammatory activation of various cell types through epigenetic and non-epigenetic mechanisms, and ameliorate pathology in a mouse model of periodontitis. Activation of gingival fibroblasts (GFs) significantly contributes to the development of periodontitis and the anaerobic bacterium Porphyromonas gingivalis plays a key role in driving chronic inflammation. Here, we analyzed the role of HDACs in inflammatory responses of GFs. Pan-HDACi suberoylanilide hydroxamic acid (SAHA) and/or ITF2357 (givinostat) significantly reduced TNFα- and P. gingivalis–inducible expression and/or production of a cluster of inflammatory mediators in healthy donor GFs ( IL1B, CCL2, CCL5, CXCL10, COX2, and MMP3) without affecting cell viability. Selective inhibition of HDAC3/6, but not specific HDAC1, HDAC6, or HDAC8 inhibition, reproduced the suppressive effects of pan-HDACi on the inflammatory gene expression profile induced by TNFα and P. gingivalis, suggesting a critical role for HDAC3 in GF inflammatory activation. Consistently, silencing of HDAC3 expression with siRNA largely recapitulated the effects of HDAC3/6i on mRNA levels of inflammatory mediators in P. gingivalis–infected GFs. In contrast, P. gingivalis internalization and intracellular survival in GFs remained unaffected by HDACi. Activation of mitogen-activated protein kinases and NFκB signaling was unaffected by global or HDAC3/6-selective HDACi, and new protein synthesis was not required for gene suppression by HDACi. Finally, pan-HDACi and HDAC3/6i suppressed P. gingivalis–induced expression of IL1B, CCL2, CCL5, CXCL10, MMP1, and MMP3 in GFs from patients with periodontitis. Our results identify HDAC3 as an important regulator of inflammatory gene expression in GFs and suggest that therapeutic targeting of HDAC activity, in particular HDAC3, may be clinically beneficial in suppressing inflammation in periodontal disease.

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