論文 - 詳細
| RRC ID | 38297 |
|---|---|
| 著者 | Yamashiro K, Sasano T, Tojo K, Namekata I, Kurokawa J, Sawada N, Suganami T, Kamei Y, Tanaka H, Tajima N, Utsunomiya K, Ogawa Y, Furukawa T. |
| タイトル | Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
There is considerable evidence indicating that intracellular Ca2+ participates as a second messenger in TLR4-dependent signaling. However, how intracellular free Ca2+ concentrations ([Ca2+]i) is increased in response to LPS and how they affect cytokine production are poorly understood. Here we examined the role of transient receptor potential (TRP), a major Ca2+ permeation pathway in non-excitable cells, in the LPS-induced cytokine production in macrophages. Pharmacologic experiments suggested that TRPV family members, but neither TRPC nor TRPM family members, are involved in the LPS-induced TNFalpha and IL-6 production in RAW264 macrophages. RT-PCR and immunoblot analyses showed that TRPV2 is the sole member of TRPV family expressed in macrophages. ShRNA against TRPV2 inhibited the LPS-induced TNFalpha and IL-6 production as well as IkappaBalpha degradation. Experiments using BAPTA/AM and EGTA, and Ca2+ imaging suggested that the LPS-induced increase in [Ca2+]i involves both the TRPV2-mediated intracellular and extracellular Ca2+ mobilizations. BAPTA/AM abolished LPS-induced TNFalpha and IL-6 production, while EGTA only partially suppressed LPS-induced IL-6 production, but not TNFalpha production. These data indicate that TRPV2 is involved in the LPS-induced Ca2+ mobilization from intracellular Ca2+ store and extracellular Ca2+. In addition to Ca2+ mobilization through the IP3-receptor, TRPV2-mediated intracellular Ca2+ mobilization is involved in NFkappaB-dependent TNFalpha and IL-6 expression, while extracellular Ca2+ entry is involved in NFkappaB-independent IL-6 production. |
| 巻・号 | 398(2) |
| ページ | 284-9 |
| 公開日 | 2010-7-23 |
| DOI | 10.1016/j.bbrc.2010.06.082 |
| PII | S0006-291X(10)01208-8 |
| PMID | 20599720 |
| MeSH | Animals Calcium / metabolism* Calcium Channels / genetics Calcium Channels / physiology* Cell Line Cytokines / biosynthesis* Egtazic Acid / analogs & derivatives Egtazic Acid / pharmacology Gene Knockdown Techniques I-kappa B Proteins / metabolism Lipopolysaccharides / immunology Macrophages / immunology* Mice NF-KappaB Inhibitor alpha TRPV Cation Channels / genetics TRPV Cation Channels / physiology* |
| IF | 2.985 |
| 引用数 | 54 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |