scholarly journals Causal effects of inflammatory protein biomarkers on inflammatory diseases

2021 ◽  
Vol 7 (50) ◽  
Author(s):  
Weronica E. Ek ◽  
Torgny Karlsson ◽  
Julia Höglund ◽  
Mathias Rask-Andersen ◽  
Åsa Johansson
Keyword(s):  
Inflammatory Diseases ◽  
Causal Effects ◽  
Protein Biomarkers ◽  
Inflammatory Protein

scholarly journals HIF-1α regulates epithelial inflammation by cell autonomous NFκB activation and paracrine stromal remodeling

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3343-3354 ◽  
Author(s):  
Marzia Scortegagna ◽  
Christophe Cataisson ◽  
Rebecca J. Martin ◽  
Daniel J. Hicklin ◽  
Robert D. Schreiber ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cancer Metastasis ◽  
Inflammatory Diseases ◽  
Hypoxia Inducible Factor ◽  
Local Environment ◽  
Inflammatory Cells ◽  
Hypoxia Inducible Factor 1 ◽  
Inflammatory Protein ◽  
Multiple Cell ◽  
Epithelial Inflammation

AbstractHypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non–cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor κ B (NFκB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1–induced NFκB activation was composed of 2 elements, IκB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFκB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFα) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFα immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFκB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression.

scholarly journals Fcγ Receptor I- and III-Mediated Macrophage Inflammatory Protein 1α Induction in Primary Human and Murine Microglia

2002 ◽  
Vol 70 (9) ◽  
pp. 5177-5184 ◽  
Author(s):  
Xianyuan Song ◽  
Scott Shapiro ◽  
David L. Goldman ◽  
Arturo Casadevall ◽  
Matthew Scharff ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Pyrrolidine Dithiocarbamate ◽  
Wild Type ◽  
Human Microglia ◽  
Downstream Signaling ◽  
Inflammatory Protein ◽  
Α Chain ◽  
Macrophage Inflammatory Protein

ABSTRACT Microglial cell phagocytic receptors may play important roles in the pathogenesis and treatment of several neurological diseases. We studied microglial Fc receptor (FcR) activation with respect to the specific FcγR types involved and the downstream signaling events by using monoclonal antibody (MAb)-coated Cryptococcus neoformans immune complexes as the stimuli and macrophage inflammatory protein 1α (MIP-1α) production as the final outcome. C. neoformans complexed with murine immunoglobulin G (IgG) of γ1, γ2a, and γ3, but not γ2b isotype, was effective in inducing MIP-1α in human microglia. Since murine γ2b binds to human FcγRII (but not FcγRI or FcγRIII), these results indicate that FcγRI and/or FcγRIII is involved in MIP-1α production. Consistent with this, an antibody that blocks FcγRII (IV.3) failed to inhibit MIP-1α production, while an antibody that blocks FcγRIII (3G8) did. An anti-C. neoformans MAb, 18B7 (IgG1), but not its F(ab′)2, induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase kinase phosphorylation, and MIP-1α release was suppressed by the ERK inhibitor U0126. C. neoformans plus 18B7 also induced degradation of I-κBα, and MIP-1α release was suppressed by the antioxidant NF-κB inhibitor pyrrolidine dithiocarbamate. To confirm the role of FcR more directly, we isolated microglia from wild-type and various FcR-deficient mice and then challenged them with C. neoformans plus 18B7. While FcγRII-deficient microglia showed little difference from the wild-type microglia, both FcγRI α-chain- and FcγRIII α-chain-deficient microglia produced less MIP-1α, and the common Fc γ-chain-deficient microglia showed no MIP-1α release. Taken together, our results demonstrate a definitive role for FcγRI and FcγRIII in microglial chemokine induction and implicate ERK and NF-κB as the signaling components leading to MIP-1α expression. Our results delineate a new mechanism for microglial activation and may have implications for central nervous system inflammatory diseases.

scholarly journals DNA methylation proxies for 16 plasma proteins predict the incidence of 7 leading causes of morbidity

2020 ◽  
Author(s):  
Danni A Gadd ◽  
Robert F Hillary ◽  
Daniel L McCartney ◽  
Anna J Stevenson ◽  
Cliff Nangle ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Plasma Proteins ◽  
Multiple Testing ◽  
Disease Risk ◽  
Common Disease ◽  
Protein Biomarkers ◽  
Inflammatory Protein ◽  
Generation Scotland ◽  
Lothian Birth Cohort

AbstractChronic morbidities place longstanding burdens on our health as we age. Although protein biomarkers are critical for the early detection of such diseases, current studies are limited by low sample sizes, variability in proteomics methods and fluctuations in inflammatory protein expression. Here, we present a novel framework for protein-by-proxy analysis of incident disease. We show that DNA methylation proxies for nine inflammatory and seven neurology plasma proteins (generated in up to 875 individuals in the Lothian Birth Cohort 1936) predict the incidence of seven leading causes of morbidity in the Generation Scotland cohort (n=9,537), ascertained via electronic health data linkage over a follow-up period of up to 14 years. After correction for multiple testing and adjustment for common disease risk factors, these included proxy associations between CCL11 and depression (Hazard Ratio: HR = 1.45, P = 1.8 x 10-4), VEGFA and ischaemic heart disease (HR = 1.16, P = 0.02) and associations between incident diabetes and FGF-21 (HR = 1.39, P = 9.7 x 10-7), NEP (HR = 1.32, P = 2.8 x 10-6) and N-CDase (HR = 1.16, P = 0.02). Several of the protein-proxy associations with disease pinpoint proteins that are already therapeutic targets for the diseases in question. These results provide new opportunities to identify circulating biomarkers for disease detection and candidate pathways for drug targeting.

scholarly journals Protein Biomarkers in Uveitis

2020 ◽  
Vol 11 ◽  
Author(s):  
Reema Bansal ◽  
Amod Gupta
Keyword(s):  
Biomarker Discovery ◽  
Inflammatory Diseases ◽  
Protein Composition ◽  
Proteome Analysis ◽  
Protein Biomarkers ◽  
Blood Retinal Barrier ◽  
Clinical Appearance ◽  
Ocular Fluids ◽  
A Cell ◽  
Work Done

The diseases affecting the retina or uvea (iris, ciliary body, or choroid) generate changes in the biochemical or protein composition of ocular fluids/tissues due to disruption of blood-retinal barrier. Ocular infections and inflammations are sight-threatening diseases associated with various infectious and non-infectious etiologies. Several etiological entities cause uveitis, a complex intraocular inflammatory disease. These causes of uveitis differ in different populations due to geographical, racial, and socioeconomic variations. While clinical appearance is sufficiently diagnostic in many diseases, some of the uveitic entities manifest nonspecific or atypical clinical presentation. Identification of biomarkers in such diseases is an important aid in their diagnostic armamentarium. Different diseases and their different severity states release varying concentrations of proteins, which can serve as biomarkers. Proteomics is a high throughput technology and a powerful screening tool for serum biomarkers in various diseases that identifies proteins by mass spectrometry and helps to improve the understanding of pathogenesis of a disease. Proteins determine the biological state of a cell. Once identified as biomarkers, they serve as future diagnostic and pharmaceutical targets. With a potential to redirect the diagnosis of idiopathic uveitis, ocular proteomics provide a new insight into the pathophysiology and therapeutics of various ocular inflammatory diseases. Tears, aqueous and vitreous humor represent potential repositories for proteomic biomarkers discovery in uveitis. With an extensive proteomics work done on animal models of uveitis, various types of human uveitis are being subjected to proteome analysis for biomarker discovery in different ocular fluids (vitreous, aqueous, or tears).

Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica

2012 ◽  
Vol 19 (7) ◽  
pp. 926-931 ◽  
Author(s):  
Honghao Wang ◽  
Kai Wang ◽  
Conghui Wang ◽  
Xiaonan Zhong ◽  
Wei Qiu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Vascular Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pentraxin 3 ◽  
Inflammatory Protein ◽  
Ptx3 Level ◽  
Headache Patients

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune-mediated inflammatory diseases of the central nervous system. In the acute phase of these diseases, secondary ischemia due to inflammation-induced endothelial dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro-inflammatory protein and a novel biomarker of inflammatory vascular diseases. Objective: We aimed to determine whether PTX3 levels are elevated in MS and NMO patients. Methods: The concentrations of plasma PTX3 were measured using an enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer controls. Results: During relapse, plasma PTX3 levels were higher in MS patients than in headache patients ( p=0.003) and controls ( p<0.001). Plasma PTX3 levels were also increased in NMO patients compared with CI patients ( p=0.011), headache patients ( p<0.001) and controls ( p<0.001). CI patients showed elevated PTX3 levels compared with controls ( p=0.008). MS and NMO patients showed a trend toward an increased disease disability with higher plasma PTX3 during relapse (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). Conclusion: Plasma PTX3 level is associated with inflammatory responses in MS and NMO.

scholarly journals Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Chin-Wei Chiang ◽  
Hsueh-Te Lee ◽  
Der-Cherng Tarng ◽  
Ko-Lin Kuo ◽  
Li-Ching Cheng ◽  
...  
Keyword(s):  
Epoxide Hydrolase ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Interleukin 1 ◽  
Kidney Injury ◽  
Soluble Epoxide Hydrolase ◽  
Obstructive Nephropathy ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Renal Tubular

Soluble epoxide hydrolase (sEH) is abundantly expressed in kidney and plays a potent role in regulating inflammatory response in inflammatory diseases. However, the role of sEH in progression of chronic kidney diseases such as obstructive nephropathy is still elusive. In current study, wild-type (WT) andsEHdeficient (sEH−/−) mice were subjected to the unilateral ureteral obstruction (UUO) surgery and the kidney injury was evaluated by histological examination, western blotting, and ELISA. The protein level of sEH in kidney was increased in UUO-treated mice group compared to nonobstructed group. Additionally, UUO-induced hydronephrosis, renal tubular injury, inflammation, and fibrosis were ameliorated insEH−/−mice with the exception of glomerulosclerosis. Moreover,sEH−/−mice with UUO showed lower levels of inflammation-related and fibrosis-related protein such as monocyte chemoattractant protein-1, macrophage inflammatory protein-2, interleukin-1β(IL-1β), IL-6, inducible nitric oxide synthase, collagen 1A1, andα-actin. The levels of superoxide anion radical and hydrogen peroxide as well as NADPH oxidase activity were also decreased in UUO kidneys ofsEH−/−mice compared to that observed in WT mice. Collectively, our findings suggest that sEH plays an important role in the pathogenesis of experimental obstructive nephropathy and may be a therapeutic target for the treatment of obstructive nephropathy-related diseases.

Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice

2004 ◽  
Vol 91 (06) ◽  
pp. 1194-1201 ◽  
Author(s):  
Ken-ichiro Inoue ◽  
Rie Yanagisawa ◽  
Miho Sakurai ◽  
Akinori Shimada ◽  
Takehito Morita ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Intraperitoneal Administration ◽  
Pulmonary Hemorrhage ◽  
Protective Role ◽  
Protein Levels ◽  
Proinflammatory Mediators ◽  
Lps Challenge ◽  
Inflammatory Protein ◽  
Significant Prolongation

SummaryAlthough the role of interleukin (IL)-6 in inflammatory diseases has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remains to be established. The present study elucidated the role of IL-6 in hemostatic and coagulatory changes during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS: 1 mg/kg) using IL-6 null (-/-) mice. After LPS challenge, IL-6 (-/-) mice revealed significant prolongation of prothrombin time and activated partial thromboplastin time and a significant decrease in platelet counts as compared with wild type mice. LPS treatment induced marked pulmonary hemorrhage with neutrophilic inflammation in IL-6 (-/-) mice, in contrast, only mild neutrophilic infiltration in WT mice confirmed by macroscopic and histological findings.The protein levels of proinflammatory mediators, such as IL-1?, macrophage inflammatory protein (MIP)-1a., MIP-2, macrophage chemoattractant protein1, granulocyte/macrophage-colony-stimulating factor, and keratinocyte chemoattractant in the lungs were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory processes.

scholarly journals Selenium and Copper as Biomarkers for Pulmonary Arterial Hypertension in Systemic Sclerosis

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1894 ◽  
Author(s):  
Qian Sun ◽  
Julian Hackler ◽  
Julia Hilger ◽  
Hans Gluschke ◽  
Aldina Muric ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Diagnostic Marker ◽  
Inflammatory Diseases ◽  
Severe Disease ◽  
Diagnostic Value ◽  
Protein Biomarkers ◽  
Pulmonary Arterial ◽  
Se Status

Circulating selenoprotein P (SELENOP) constitutes an established biomarker of Se status. SELENOP concentrations are reduced in inflammation and severe disease. Recently, elevated SELENOP levels have been suggested as diagnostic marker and therapeutic target in pulmonary arterial hypertension (PAH). We decided to re-evaluate this hypothesis. A group of healthy controls (n = 30) was compared with patients suffering from systemic sclerosis (SSc, n = 66), one third with SSc-related PAH. Serum was analysed for trace elements and protein biomarkers, namely SELENOP, glutathione peroxidase 3 (GPx3) and ceruloplasmin (CP). Compared to controls, patients with SSc-related PAH displayed reduced serum Se (91 ± 2 vs. 68 ± 2 µg/L) and SELENOP concentrations (3.7 ± 0.8 vs. 2.7 ± 0.9 mg/L), along with lower GPx3 activity (278 ± 40 vs. 231 ± 54 U/L). All three biomarkers of Se status were particularly low in patients with skin involvement. Serum Cu was not different between the groups, but patients with SSc-related PAH showed elevated ratios of Cu/Se and CP/SELENOP as compared to controls. Our data indicate that patients with SSc-related PAH are characterized by reduced Se status in combination with elevated CP, in line with other inflammatory diseases. Further analyses are needed to verify the diagnostic value of these TE-related biomarkers in PAH.

scholarly journals Integrated Haematological Profiles of RedoxStatus, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Carla Lubrano ◽  
Giuseppe Valacchi ◽  
Palma Specchia ◽  
Lucio Gnessi ◽  
Elizaveta P. Rubanenko ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Plasminogen Activator Inhibitor ◽  
Monounsaturated Fatty Acids ◽  
Glutathione S Transferase ◽  
Protein Biomarkers ◽  
Plasminogen Activator Inhibitor 1 ◽  
Inflammatory Protein ◽  
Target Organs ◽  
Membrane Bound ◽  
Leukocyte Chemotaxis

The pathogenesis of obesity (OB) and metabolic syndrome (MetS) implies free radical-, oxidized lipid- (LOOH-), and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS) and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS) evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA). Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues.

Sign in / Sign up

Export Citation Format

Share Document