scholarly journals Extracellular Secretion of Suppressor of Cytokine Signaling (SOCS) Proteins by Alveolar Macrophages (AMs)

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Emilie Bourdonnay ◽  
Loka Raghu Kumar Penke ◽  
Marc Peters‐Golden
Keyword(s):  
Alveolar Macrophages ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Extracellular Secretion ◽  
Socs Proteins

scholarly journals 2165 Vesicular secretion of suppressor of cytokine signaling 3 by alveolar macrophages is dysregulated in NSCLC patients and its provision inhibits epithelial cell transformation and tumor cell function

2018 ◽  
Vol 2 (S1) ◽  
pp. 36-36
Author(s):  
Jennifer Speth ◽  
Loka R. Penke ◽  
Joseph Bazzill ◽  
Douglas A. Arenberg ◽  
James J. Moon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Alveolar Macrophages ◽  
Cell Transformation ◽  
Soft Agar ◽  
Cigarette Smoke Extract ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Induced Apoptosis ◽  
Nsclc Patients

OBJECTIVES/SPECIFIC AIMS: Insufficient endogenous expression of suppressor of cytokine signaling 3 (SOCS3) with subsequent over-activation of its target, the transcription factor STAT3, has been associated with tumorigenesis and cancer development in the lung and other organs. We have observed that a “backup” source of SOCS3 in the lung, namely that secreted in microvesicles (MVs) by alveolar macrophages, is reduced in the bronchoalveolar lavage fluid (BALF) of KRAS mutant mice harboring lung tumors. Here we sought to evaluate levels of SOCS3 in BALF of a cohort of non-small cell lung cancer (NSCLC) patients and to test the effects of vesicular SOCS3 administration on tumor cell transformation and function as potential therapeutic strategy. METHODS/STUDY POPULATION: In total, 22 BALF samples were obtained from healthy volunteers (n=11) as well as patients undergoing diagnostic bronchoscopies for suspected lung cancer (n=11). SOCS3 levels in the BALF were determined by ELISA after brief sonication to disrupt vesicles. In vitro experiments utilized the human adenocarcinoma cell line (A549) or human G12V mutant KRAS-expressing rat lung epithelial cells (RLE-G12V). Proliferation, Fas ligand (FasL)-induced apoptosis, and chemical transformation with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or cigarette smoke extract (CSE) were assessed by CyQuant assay, annexin V staining, and soft agar assay, respectively. For SOCS3 rescue, epithelial cells were treated with natural alveolar macrophages-derived MVs (isolated via ultracentrifugation) or synthetic unilamellar liposomes containing human recombinant SOCS3 for at least 1 hour before assay. RESULTS/ANTICIPATED RESULTS: SOCS3 levels were significantly reduced in BALF samples of patients determined to have NSCLC as compared with healthy volunteers (186.6±26.74 vs. 395.6±74.31 pg/mL, p=0.015, n=11). Addition of exogenous SOCS3-containing liposomes had the capacity to significantly inhibit MNNG and cigarette smoke extract-induced transformation and colony formation in soft agar. Exogenous SOCS3 provided in liposomes or in natural MVs significantly induced apoptosis (both in the presence and absence of FasL) and inhibited basal proliferation of A549 cells. DISCUSSION/SIGNIFICANCE OF IMPACT: These data identified a novel dysregulation of immune surveillance in the form of decreased SOCS3 secretion in the tumor-bearing lung that may contribute to tumorigenesis via sustained STAT3 activation. Future studies will focus on the mechanism underlying this defect and whether rescuing SOCS3 secretion can inhibit cancer progression in vivo.

Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Amira Alkharusi ◽  
Mercedes Mirecki-Garrido ◽  
Zuheng Ma ◽  
Fahad Zadjali ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Type I ◽  
Suppressor Of Cytokine Signaling ◽  
Β Cell ◽  
Diabetes In Mice ◽  
Socs Proteins ◽  
Stat Pathway

AbstractDiabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity.The elevated sensitivity of SOCS2We show that 6-month-old SOCS2Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of β-cell survival may be of relevance to islet regeneration and survival in transplantation.

Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells

2016 ◽  
Vol 306-307 ◽  
pp. 41-52 ◽  
Author(s):  
Feras M. Ghazawi ◽  
Elliott M. Faller ◽  
Parmvir Parmar ◽  
Abdulkareem El-Salfiti ◽  
Paul A. MacPherson
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Target Surface ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Socs Proteins

Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins

Immunobiology ◽  
2008 ◽  
Vol 213 (3-4) ◽  
pp. 225-235 ◽  
Author(s):  
Alexander Dalpke ◽  
Klaus Heeg ◽  
Holger Bartz ◽  
Andrea Baetz
Keyword(s):  
Innate Immunity ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Socs Proteins

scholarly journals Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingyu Sun ◽  
Chuangang Tang ◽  
Jun Liu ◽  
Wenli Jiang ◽  
Haifeng Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Prognostic Factor ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Expression Levels ◽  
Pathway Enrichment ◽  
Stat Signaling ◽  
Socs Proteins ◽  
Mrna Expression Levels

Abstract Background Abnormal expression of suppressor of cytokine signaling (SOCS) proteins regulates tumor angiogenesis and development in cancers. In this study, we aimed to perform a comprehensive bioinformatic analysis of SOCS proteins in breast invasive carcinoma (BRCA). Methods The gene expression, methylation level, copy number, protein expression and patient survival data related to SOCS family members in BRCA patients were obtained from the following databases: Oncomine, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), PCViz, cBioPortal and Kaplan-Meier plotter. Correlation analyses, identification of interacting genes and construction of regulatory networks were performed by functional and pathway enrichment analyses, weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Results Data related to 1109 BRCA tissues and 113 normal breast tissue samples were extracted from the TCGA database. SOCS2 and SOCS3 exhibited significantly lower mRNA expression levels in BRCA tissues than in normal tissues. BRCA patients with high mRNA levels of SOCS3 (p < 0.01) and SOCS4 (p < 0.05) were predicted to have significantly longer overall survival (OS) times. Multivariate analysis showed that SOCS3 was an independent prognostic factor for OS. High mRNA expression levels of SOCS2 (p < 0.001), SOCS3 (p < 0.001), and SOCS4 (p < 0.01), and a low expression level of SOCS5 (p < 0.001) were predicted to be significantly associated with better recurrence-free survival (RFS). Multivariate analysis showed that SOCS2 was an independent prognostic factor for RFS. Lower expression levels of SOCS2 and SOCS3 were observed in patients with tumors of more advanced clinical stage (p < 0.05). Functional and pathway enrichment analyses, together with WGCNA and GSEA, showed that SOCS3 and its interacting genes were significantly involved in the JAK-STAT signaling pathway, suggesting that JAK-STAT signaling might play a critical role in BRCA angiogenesis and development. Western blot results showed that overexpression of SOCS3 inhibited the activity of the JAK-STAT signaling pathway in vitro. Conclusions SOCS family proteins play a very important role in BRCA. SOCS3 may be a prognostic factor and SOCS2 may be a potential therapeutic target in breast cancer.

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