Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Yamada, Tetsuji; Fujieda, Shigeharu; Yanagi, Shigeru; Yamamura, Hirohei; Inatome, Ryoko; Sunaga, Hiroshi; Saitô, Hitoshi

doi:10.4049/jimmunol.166.1.538

Cited by 51 publications

(37 citation statements)

References 52 publications

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“…No contamination of epithelial cells was confirmed by immunohistochemical examination with cytokeratin marker. There was wide variation in the expression of Syk by nasal fibroblast lines as described previously (4). Before starting the experiments, Western blot analysis was performed to be determined Syk expression in fibroblast cell line.…”

Section: Cell Preparationmentioning

confidence: 99%

IL-1 Induced Chemokine Production Through the Association of Syk with TNF Receptor-Associated Factor-6 in Nasal Fibroblast Lines

Yamada

Fujieda

Yanagi

et al. 2001

The Journal of Immunology

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The fibroblasts stimulated by cytokines released the chemokine and recruited the infiltrating cells, including eosinophils, that play a key role in the pathogenesis of airway disease. We established the human fibroblast lines showing high Syk expression and the lines showing low Syk expression from pieces of nasal polyp. IL-1 induces the interaction of TNFR-associated factor (TRAF) 6 with IL-1R-associated kinase, which is rapidly recruited to the IL-1R after IL-1 induction, whereas TRAF2 participates in TNF-α-signaling. In the present study, we found that Syk played a different role in IL-1- and TNF-α-induced chemokine production through a signaling complex involving Syk and TRAF6. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with IL-1. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production in response to IL-1. However, the change of Syk expression did not affect RANTES production by TNF-α stimulation. We concluded that Syk is required for the IL-1-induced chemokine production through the association with TRAF-6 in fibroblasts of nasal polyps.

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Section: Cell Preparationmentioning

confidence: 99%

IL-1 Induced Chemokine Production Through the Association of Syk with TNF Receptor-Associated Factor-6 in Nasal Fibroblast Lines

Yamada

Fujieda

Yanagi

et al. 2001

The Journal of Immunology

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“…In addition, Syk has been detected in fibroblasts (2,3), epithelial cells (4), and breast tissues (5). In endothelial cells, it plays a key role in proliferation, migration, and developmental angiogenesis/lymphangiogenesis (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck

et al. 2007

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Syk, a non-receptor tyrosine kinase, is an important component of immunoreceptor signaling in hematopoietic cells. It has been implicated in key regulatory pathways including phosphoinositide 3-kinase and phospholipase C; (PLC;) activation in B cells and integrin signaling in platelets and bronchial epithelial cells. Recently, potential roles in cancer have been reported. In breast cancers, reduced Syk expression was associated with invasion, and its overexpression in cell lines was shown to inhibit cell motility. In contrast, Syk has been shown to mediate chemomigration in nasopharyngeal carcinoma cells. Its role in squamous cell carcinomas of the head and neck (SCCHN) has not yet been investigated. Syk mRNA and protein expression was detected in 6 of 10 SCCHN cell lines. When Syk was transfected into Syknegative cells (SIHN-011A), chemomigration was enhanced in vitro and this was associated with activation of PLC;1. Conversely, abrogation of Syk activity by pharmacologic inhibition or small interfering RNA in HN6 cells with high levels of endogenous expression inhibited migration, haptotaxis, and engagement with matrix proteins; this was accompanied by decreased levels of phosphorylated AKT. Similar effects were seen in Syk-positive CAL 27 cells but not in Syk-negative SIHN-011A cells. Immunoprecipitation suggested co-association of Syk with epidermal growth factor receptor and GRB-2. Syk expression in SCCHN patient tissues was examined by semiquantitative real-time PCR (n = 45) and immunohistochemistry (n = 38) in two independent cohorts. Higher levels of Syk expression were observed in tumors and lymph node metastases relative to normal tissues. High Syk expression significantly correlated with worse survival and may be of prognostic value in SCCHN due to its potential role in cell migration and invasion. [Cancer Res 2007;67(16):7907-16]

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“…It is also expressed in human mammary (Coopman et al, 2000) and airway epithelial cells (Ulanova et al, 2005), nasal fibroblasts (Yamada et al, 2001) and hepatocytes (Tsuchida et al, 2000). These results suggest that Syk plays a general physiological role in nonhaematopoietic cells as well.…”

Section: Discussionmentioning

confidence: 67%

Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk

Inubushi

Nagano-Fujii

Kitayama

et al. 2008

Journal of General Virology

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Hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma. However, the precise mechanism underlying the carcinogenesis is yet to be elucidated. It has recently been reported that Syk, a non-receptor protein tyrosine kinase, functions as a potent tumour suppressor in human breast carcinoma. This study first examined the possible effect of HCV infection on expression of Syk in vivo. Immunohistochemical analysis revealed that endogenous Syk, which otherwise was expressed diffusely in the cytoplasm of normal hepatocytes, was localized near the cell membrane with a patchy pattern in HCV-infected hepatocytes. The possible interaction between HCV proteins and Syk in human hepatoma-derived Huh-7 cells was then examined. Immunoprecipitation analysis revealed that NS5A interacted strongly with Syk. Deletion-mutation analysis revealed that an N-terminal portion of NS5A (aa 1-175) was involved in the physical interaction with Syk. An in vitro kinase assay demonstrated that NS5A inhibited the enzymic activity of Syk and that, in addition to the N-terminal 175 residues, a central portion of NS5A (aa 237-302) was required for inhibition of Syk. Moreover, Syk-mediated phosphorylation of phospholipase C-c1 was downregulated by NS5A. An interaction of NS5A with Syk was also detected in Huh-7.5 cells harbouring an HCV RNA replicon or infected with HCV. In conclusion, these results demonstrated that NS5A interacts with Syk resulting in negative regulation of its kinase activity. The results indicate that NS5A may be involved in the carcinogenesis of hepatocytes through the suppression of Syk kinase activities. INTRODUCTIONHepatitis C virus (HCV) is the major aetiological agent of viral hepatitis worldwide after hepatitis A and B viruses (Choo et al., 1989), with about 170 million people being infected. The majority of HCV-infected individuals develop chronic infection, which may progress to liver cirrhosis and hepatocellular carcinoma (HCC). HCV is a member of the family Flaviviridae and its genome consists of a single-stranded, positive-sense RNA of approximately 9600 nt, which encodes a polyprotein precursor of about 3010 aa. Currently, clinical HCV isolates are classified into six genotypes and more than 60 subtypes (Doi et al., 1996;Mellor et al., 1995;Robertson et al., 1998). The polyprotein is cleaved by signal peptidase, signal peptide peptidase and two virally encoded proteases to generate at least ten mature proteins: core, envelope glycoprotein 1 (E1), E2, p7, non-structural protein 2 (NS2), NS3, NS4A, NS4B, NS5A and NS5B Reed & Rice, 2000).HCV NS5A is part of the replication complex that catalyses replication of the viral genome. NS5A takes two forms, p56 and p58, with different degrees of phosphorylation, which may play distinct roles in the virus replication cycle (Evans 3These authors contributed equally to this work. YXX(L/I)X 6-8 YXX(L/I)] in the cytoplasmic tail of the Fc receptor c-chain or B-cell receptor subunit Iga to be activated after the engagement of immune receptors (Kurosaki et al...

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Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Cited by 51 publications

References 52 publications

IL-1 Induced Chemokine Production Through the Association of Syk with TNF Receptor-Associated Factor-6 in Nasal Fibroblast Lines

IL-1 Induced Chemokine Production Through the Association of Syk with TNF Receptor-Associated Factor-6 in Nasal Fibroblast Lines

Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck

Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk

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