The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients

Tsao, Jeng‐Ting; Kuo, Chia-Chen; Lin, Szu-Yuan

doi:10.1007/s10238-008-0006-0

Cited by 27 publications

(25 citation statements)

References 45 publications

(45 reference statements)

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“…This study revealed that patients with SLE had a higher expression of SOCS1 mRNA, which was different from the results of Tsao et al 24 Tsao et al showed that SOCS1 expression was not significantly different between patients with SLE and controls. This discrepancy may be due to different methods for measurement of SOCS1 levels, and different sample sizes.…”

Section: Genotypescontrasting

confidence: 99%

Suppressor of cytokine signaling 1 gene expression and polymorphisms in systemic lupus erythematosus

Chan

et al. 2010

Lupus

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With the aim of investigating the role of suppressor of cytokine signaling 1 (SOCS1) in the pathogenesis of systemic lupus erythematosus, 107 patients with systemic lupus erythematosus, 101 healthy controls, and 151 patients with ankylosing spondylitis were enrolled in this study. SOCS1 mRNA level was measured by the method of quantitative real-time polymerase chain reaction. SOCS1 polymorphisms were detected by the polymerase chain reaction/restriction fragment length polymorphisms method. Systemic lupus erythematosus disease activity was evaluated with the SLEDAI. This study showed that the SOCS1 mRNA expression was significantly higher in the patients with systemic lupus erythematosus than in the healthy controls (p = 0.0014). Patients with active systemic lupus erythematosus had a higher expression of SOCS1 mRNA than the patients with inactive systemic lupus erythematosus (p = 0.035). There was no significant difference in the frequencies of the SOCS1-1478CA/del polymorphisms among the patients with systemic lupus erythematosus, healthy controls, and patients with ankylosing spondylitis. The genotype frequency of the SOCS1-1478 polymorphisms in the dominant model (CA/del+del/del versus CA/CA) was significantly decreased in the patients with thrombocytopenia compared with those without thrombocytopenia (p(c) = 0.035). Moreover, the allele frequency of SOCS1-1478del was also significantly lower in the patients with thrombocytopenia than in those without thrombocytopenia (p( c) = 0.02). In conclusion, this study demonstrated that the expression of SOCS1 mRNA was significantly increased in patients with systemic lupus erythematosus. Moreover, SOCS1 mRNA levels in patients with active systemic lupus erythematosus were significantly higher than those in the inactive patients. We also found that the systemic lupus erythematosus patients with thrombocytopenia have a lower frequency of SOCS1-1478del compared with patients without thrombocytopenia.

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Section: Genotypescontrasting

confidence: 99%

Suppressor of cytokine signaling 1 gene expression and polymorphisms in systemic lupus erythematosus

Chan

et al. 2010

Lupus

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“…SLE patients with active disease significantly express higher CIS transcript levels than normal individuals and SLE patients with inactive disease, whereas the difference in SOCS1, SOCS2 and SOCS3 transcript levels between normal individuals and SLE patients are not statistically significant. These data suggest that CIS can serve as an SLE disease marker and may be involved in the pathogenesis of SLE, and that TNF-α may play an important role in the regulation of CIS and SOCS2 gene expression in PBMCs in vivo [67]. In monocytes higher expression level of STAT1 proteins was shown from SLE patients compared to controls, which also positively correlated with SLEDAI.…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 64%

Toll-Like Receptor Pathways in Autoimmune Diseases

Chen

Szodoray

Zeher

2015

Clinic Rev Allerg Immunol

248

177

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Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen.Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location；the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. Particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathways regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. KEYWORDS:Toll-like receptors (TLRs); autoimmune disease; IL-1 receptor associated kinase (IRAK); TNF receptor associated factor (TRAF); Suppressor of cytokine signaling (SOCS) 3 Autoimmune diseases are characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Even though the accurate etiology and pathogenesis of the majority of these diseases are still not clear, complex elements, including genetic, environmental, hormonal factors may provoke the autoimmune processes leading to the development of the disease.Concerning the role of derailed immune responses in the pathogenesis, aberrant processes both in the innate and adaptive immune system have been shown to participate in the disease initiation and perpetuation [1]. Within these processes, numerous studies have been demonstrated that Toll-like receptors (TLRs) have an essential role in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. [2,3]. Toll-like receptorsThe innate immune system is the first line of host defense mechanisms against invading microorganisms and forms the basis of the development of adaptive immunity. Host cells express diverse pattern recognition receptors (PRRs) include toll-like receptors (TLRs), C-type lectin-like receptors (CL...

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“…Dysregulation of SOCS expression has been implicated in several inflammatory diseases, including models of multiple sclerosis (65)(66)(67)(68)(69), rheumatoid arthritis (70,71), systemic lupus erythematosus (72,73), psoriasis (74,75), type 1 diabetes (51, 76 -79), sepsis (80,81), and also in human allergic disease (82)(83)(84). Furthermore, deficiencies in SOCS1 expression have been observed in the smooth muscle in airways (85), and epithelial cells (86) of asthmatic patients and functional SOCS1 polymorphism have been correlated with the development of adult onset asthma and increased IgE levels (87,88).…”

Section: Socs1 Regulates Il-4-induced Irs-2 Signaling In Human Monocytesmentioning

confidence: 99%

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

McCormick¹,

Gowda²,

Fang³

et al. 2016

Journal of Biological Chemistry

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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 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease.Allergic asthma is an immune disorder characterized by elevation of total and specific IgE and infiltration of monocytes, lymphocytes, mast cells, eosinophils, and basophils in the lungs that causes inflammation and wheezing, cough, and dyspnea (1-4). A complex interplay of genetic and environmental factors contributes to the onset and maintenance of these diseases. Mechanistically, it is known that cytokines secreted from Th2 cells, such as interleukin (IL)-4, IL-5, IL-9, and IL-13, have a pivotal role in dictating the pathology of allergic disease (1, 2, 5, 6). The pathways by which IL-4 and IL-13 exert their biological effects have been a major focus of research and development of therapeutics to block their action through type I and II IL-4 receptors. Previously, we showed that in macrophages, IL-4 engagement of the type I IL-4 receptor resulted in robust tyrosine phosphorylation of insulin receptor substrate (IRS)-2, recruitment of p85 regulatory subunit of PI3K and GRB2, and strong induction of a subset of hallmark M2, also known as M(IL-4) (7), macrophage genes (8, 9). In contrast, IL-13 binding to the type II receptor resulted in only modest IRS-2 phosphorylation. Increasing the concentration of IL-13 did n...

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The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients

Cited by 27 publications

References 45 publications

Suppressor of cytokine signaling 1 gene expression and polymorphisms in systemic lupus erythematosus

Suppressor of cytokine signaling 1 gene expression and polymorphisms in systemic lupus erythematosus

Toll-Like Receptor Pathways in Autoimmune Diseases

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

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