論文 - 詳細
| RRC ID | 1300 |
|---|---|
| 著者 | Kato S, Yuzawa Y, Tsuboi N, Maruyama S, Morita Y, Matsuguchi T, Matsuo S. |
| タイトル | Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4. |
| ジャーナル | J Am Soc Nephrol |
| Abstract |
Acute peritonitis, in which peritoneal mesothelial cells are directly exposed to bacterial components, is a major cause of peritoneal dysfunction in continuous ambulatory peritoneal dialysis patients. We have previously shown that Toll-like receptors (TLR) are expressed in kidney cells, and LPS induces TLR4-dependent chemokine production in tubular epithelial cells. The present work was designed to investigate the involvement of TLR, especially TLR4, in the lipid A-mediated chemokine production by murine peritoneal mesothelial cells (MPMC). A primary cell culture of MPMC from C3H/HeN mice (wild-type mice; LPS sensitive) and from C3H/HeJ mice (containing a point mutation of TLR4; LPS hyposensitive) was established. The expression profile of the TLR family and their accessory molecules, CD14 and MD-2, which are requisite for the LPS signaling pathway, was examined by RT-PCR, Northern blot test, and immunohistochemical staining. Synthetic lipid A-mediated chemokine production by MPMC was studied. The involvement of MAP kinase family (ERK, JNK, and p38 mitogen-activated protein kinase) and nuclear factor (NF)-kappaB in these processes was also studied. MPMC constitutively express TLR4, CD14, and MD-2. A prominent induction of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein (MIP)-2 by MPMC was detected after lipid A stimulation and was strictly dependent on TLR4. Furthermore, TLR4-dependent chemokine production followed by leukocyte influx into the peritoneal cavity was also confirmed in vivo after stimulation with LPS. mRNA expression of MCP-1 was abolished by NF-kappaB inhibition, but were not affected by the inhibition of ERK, JNK, or p38. As compared with MCP-1, MIP-2 mRNA expression was inhibited by a high dose of curcumin but not by NF-kappaB decoy oligodeoxynucleotide and individual inhibitions of MAP kinase, suggesting that the additional signaling pathway with NF-kappaB might be involved in mRNA expression of MIP-2. These show that TLR4 is directly involved in the production of MCP-1 and MIP-2 by MPMC in a NF-kappaB-dependent manner, but the process does not require any MAP kinase activation. The results provide a candidate molecular target in prevention of it. |
| 巻・号 | 15(5) |
| ページ | 1289-99 |
| 公開日 | 2004-5-1 |
| PMID | 15100369 |
| MeSH | Animals Cell Line Cell Movement / immunology Chemokine CCL2 / genetics Chemokine CXCL2 Chemokines / genetics* Epithelium Gene Expression / drug effects Gene Expression / immunology Lipid A / pharmacology Macrophages, Peritoneal / cytology Macrophages, Peritoneal / metabolism Membrane Glycoproteins / genetics* Membrane Glycoproteins / metabolism* Mice Mice, Inbred C3H Mice, Mutant Strains Mitogen-Activated Protein Kinases / metabolism NF-kappa B / metabolism Peritoneum / cytology Peritoneum / immunology Peritoneum / metabolism* Peritonitis / chemically induced Peritonitis / metabolism* Peritonitis / pathology RNA, Messenger / metabolism Receptors, Cell Surface / genetics* Receptors, Cell Surface / metabolism* Toll-Like Receptor 4 Toll-Like Receptors Up-Regulation |
| IF | 9.274 |
| 引用数 | 73 |
| WOS 分野 | UROLOGY & NEPHROLOGY |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |