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

Abstract

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.

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

“…All these results confirm the essential role of chemokines in chemoattraction and cell guidance to the site of infection during bacterial infection. IL1 has been reported to activate chemokine production [45]. In our study, we found that IL1 was moderately up-regulated after 24 hours of stimulation and that it occupies a central position in the LPS-related network 2 providing a global image of inflammation activation (Figure 4B).…”

The Orally Available Spleen Tyrosine Kinase Inhibitor 2-[7-(3,4-Dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]nicotinamide Dihydrochloride (BAY 61-3606) Blocks Antigen-Induced Airway Inflammation in Rodents

“…In addition to these signaling cascades, much evidence has been accumulating that Syk also play a critical role in some parts of integrin signaling in neutrophils and macrophages (Vines et al, 2001;Mocsai et al, 2002). Furthermore, an essential role of Syk in IL-1-induced RANTES (regulated on activation normal T cell expressed and secreted) production in human nasal fibroblasts was suggested by an antisense experiment (Yamada et al, 2001). These data increase the value of Syk kinase inhibitor as a broad anti-inflammatory agent.…”

Proinflammatory Cytokine IL-1β Promotes Tumor Growth of Lewis Lung Carcinoma by Induction of Angiogenic Factors: In Vivo Analysis of Tumor-Stromal Interaction

“…Although many factors are considered to be angiogenic, VEGF, IL-8, and HGF are all exceptionally important and powerful inducers of angiogenesis for solid tumors and are constitutively or inductively secreted from tumor cells and/or mesenchymal stromal cells (26 -31). The stromal fibroblasts are induced to secrete HGF and VEGF by the stimulation of IL-1, basic fibroblast growth factor, and platelet-derived growth factor derived from tumor cells and macrophages in the tumor tissue (32)(33)(34)(35)(36).…”