| 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
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
