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SOCS1 Regulates IL-4-induced IRS-2 Signaling in Human Monocytes Signal Transduction
Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 d...
Source: Journal of Biological Chemistry - September 22, 2016 Category: Chemistry Authors: McCormick, S. M., Gowda, N., Fang, J. X., Heller, N. M. Tags: Immunology Source Type: research

Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome Signal Transduction
Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 d...
Source: Journal of Biological Chemistry - September 22, 2016 Category: Chemistry Authors: Sarah M. McCormick, Nagaraj Gowda, Jessie X. Fang, Nicola M. Heller Tags: Immunology Source Type: research

HO-1 Suppresses Th17-mediated Neutrophilic Airway Inflammation Immunology
Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions. However, its role in NEA is still unclear. Here, we explore the role of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin protoporphyrin IX was injected intraperitoneally into ovalbumin-challenged DO11.10 mice. Sm...
Source: Journal of Biological Chemistry - November 29, 2013 Category: Chemistry Authors: Zhang, Y., Zhang, L., Wu, J., Di, C., Xia, Z. Tags: Immunology Source Type: research

Molecules, Vol. 22, Pages 139: Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue re...
Source: Molecules - January 16, 2017 Category: Chemistry Authors: Wupeng Liao Jinrui Dong Hong Peh Lay Tan Kah Lim Li Li Wai-Shiu Wong Tags: Review Source Type: research

Molecules, Vol. 25, Pages 6028: The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway
This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagoni...
Source: Molecules - December 19, 2020 Category: Chemistry Authors: Su-Lim Kim Hack Sun Choi Ji-Hyang Kim Dong-Sun Lee Tags: Article Source Type: research

RNAi in Clinical Studies.
Abstract RNA interference (RNAi) is an efficient process of posttranscriptional gene silencing. In recent years it has been developed into a new technology in biopharmaceutical fields of science. RNAi products include short interference RNA (siRNA) but also short hairpin RNA (shRNA), bifunctional short hairpin RNA (bi-shRNA) and microRNA (miRNA). They combine with homologous fragments of the mRNA and cause its degradation. It results in inhibition of protein synthesis, or in mutation in the gene encoding it. RNAi has been used in analysis of genomes and creation of new animal models to test drugs. From the pharmac...
Source: Current Medicinal Chemistry - May 1, 2013 Category: Chemistry Authors: Kubowicz P, Zelaszczyk D, Pekala E Tags: Curr Med Chem Source Type: research