Circulating Cytokines in Primary Sjögren's Syndrome Determined by a Multiplex Cytokine Array System

Szodoray, Péter; Alex, Philip; Brun, Johan G.; Centola, Michael; Jönsson, Roland

doi:10.1111/j.0300-9475.2004.01432.x

Cited by 157 publications

(116 citation statements)

References 11 publications

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“…The concentrations of HGF, TGF-a, HBEGF in the conditioned medium were analyzed by using Luminex technology (29) analysis with multiplex beads suspension array plates according to the manufacturer's instructions (Invitrogen). Assays were done in triplicate.…”

Section: Evaluation Of Growth Factor Secretionmentioning

confidence: 99%

Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

Troiani

Martinelli

Napolitano

et al. 2013

Clinical Cancer Research

130

145

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Purpose: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is an effective treatment for patients with KRAS wild-type metastatic colorectal cancer (mCRC), its clinical use is limited by onset of resistance.Experimental Design: We characterized two colorectal cancer models to study the mechanisms of acquired resistance to cetuximab.Results: Following chronic treatment of nude mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival signals were constitutively active despite EGFR inhibition by cetuximab treatment. Whole gene expression profiling identified a series of genes involved in the hepatocyte growth factor (HGF)-MET-dependent pathways, whichwere upregulated in GEO-CR cells.Furthermore,activated, phosphorylated MET was detected in GEO-CR cells. A second colorectal cancer cell line with acquired resistance to cetuximab was obtained (SW48-CR). Inhibition of MET expression by siRNA restored cetuximab sensitivity in GEO-CR and SW48-CR cells, whereas exogenousactivation ofMETbyHGFstimulationin cetuximab-sensitiveGEOandSW48cells inducedresistance to cetuximab. Treatment of GEO-CR and SW48-CR cells with PHA665752, a selective MET inhibitor, inhibited cell growth, proliferation, and survival signals and impaired cancer cell migration. Overexpression of TGF-a, a specific EGFR ligand, was involved in the acquisition of cetuximab resistance in GEO-CR and SW48-CR cells. In fact, TGF-a overexpression induced the EGFR-MET interaction, with subsequent MET phosphorylation and activation of MET downstream effectors in GEO-CR and SW48-CR cells.Conclusions: These results suggest that overexpression of TGF-a through induction of EGFR-MET interaction contributes to cetuximab resistance in colorectal cancer cells. The combined inhibition of EGFR and MET receptor could represent a strategy for preventing and/or overcoming cetuximab resistance in patients with colorectal cancer.

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Section: Evaluation Of Growth Factor Secretionmentioning

confidence: 99%

Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

Troiani

Martinelli

Napolitano

et al. 2013

Clinical Cancer Research

130

145

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“…Multiplex bead analysis offers simultaneous quantification of cytokines, growth factors, chemokines, neurotrophic factors, and neuropeptides, either singly, or in multiplexed assays in serum [20], plasma [35], synovial fluid [36], peripheral blood mononuclear cell supernatants [37], vitreous fluid [26], and tear [38] with limited sample volume. Maier et al [29] suggested that multiplex bead analysis and Enzyme-Linked Immunosorbent Assay (ELISA) are highly correlated for measurement of cytokines in serum and vitreous and this technology is more rapid and cost effective than ELISA.…”

Section: Discussionmentioning

confidence: 99%

Effect of Adipose Tissue-Derived Inflammatory and Proangiogenic Cytokines on Proliferative Diabetic Retinopathy

Yabanoglu¹

2014

Turk J Bioch

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Objective: To determine the vitreous and serum concentrations of TNF-α, IL-6, VEGF, IL-1β, IL-8, IL-17, MCP-1, IL-1Ra, IL-10 in patients with proliferative diabetic retinopathy (PDR) and to investigate the effect of adipose tissue on the pathogenesis of PDR. Methods: Twenty-two patients with PDR were prospectively evaluated. Seven cadavers and 11 patients with idiopathic epiretinal membrane or macular hole served as the controls. Multiplex bead array technology was employed to assess the concentrations of the cytokines. Results: The intravitreal levels of VEGF, IL-8, IL-6 were significantly higher in PDR group than control groups. In PDR group, the levels of IL-17, IL-8, IL-6 were significantly elevated in the vitreous, whereas the intravitreal levels of IL-10, IL-1Ra were found to be significantly lower than the serum concentrations. No significant correlation was found between cytokine levels and body mass index (BMI), fasting blood glucose (FBG), or glycated haemoglobin (HbA1c) of diabetic patients. Conclusion:In PDR the balance between the intravitreal pro-and anti-inflammatory adipocytokines is disturbed in favor of proinflammatory and proangiogenic cytokines in the vitreous humour. This study supports the role of adipocytokines in vascular pathology in PDR. It seems that PDR is a local inflammatory disease. However, obesity may not be the root of the inflammatory mediators in PDR.

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“…In order to assess whether a shift in the cytokine homeostasis exists in autoimmune conditions, fueling the predominance of pro-inflammatory cells vs. immunoregulatory T-cells, we have measured a broad spectrum of circulating cytokines in patients with various systemic autoimmune and rheumatic diseases [36][37][38][39][40][41]. The clinical picture and immunocompetent-cell distribution of pSS Primary Sjögren's syndrome (pSS) is a chronic, slowly progressive, systemic autoimmune disease that predominantly affecting middle-aged women, although it can be seen in people of all ages, including children [42].…”

Section: Th17 Cells and The Th17/treg Ratio In Systemic Autoimmune DImentioning

confidence: 99%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one-third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions a quantitative and qualitative impairment of regulatory T cells have been shown previously and in parallel a relative dominance of proinflammatory Th17 cells has been introduced. Moreover the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T-cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of IL-6, IL-12, IL-17, IL-23 and IFN- were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression towards serious systemic autoimmune diseases. Moreover, the early-targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.

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Circulating Cytokines in Primary Sjögren's Syndrome Determined by a Multiplex Cytokine Array System

Cited by 157 publications

References 11 publications

Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

Effect of Adipose Tissue-Derived Inflammatory and Proangiogenic Cytokines on Proliferative Diabetic Retinopathy

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

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