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Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4.
J Am Soc Nephrol. 2004 May; 15(5):1289-99.JA

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.

Authors+Show Affiliations

Division of Clinical Immunology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15100369

Citation

Kato, Sawako, et al. "Endotoxin-induced Chemokine Expression in Murine Peritoneal Mesothelial Cells: the Role of Toll-like Receptor 4." Journal of the American Society of Nephrology : JASN, vol. 15, no. 5, 2004, pp. 1289-99.
Kato S, Yuzawa Y, Tsuboi N, et al. Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4. J Am Soc Nephrol. 2004;15(5):1289-99.
Kato, S., Yuzawa, Y., Tsuboi, N., Maruyama, S., Morita, Y., Matsuguchi, T., & Matsuo, S. (2004). Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4. Journal of the American Society of Nephrology : JASN, 15(5), 1289-99.
Kato S, et al. Endotoxin-induced Chemokine Expression in Murine Peritoneal Mesothelial Cells: the Role of Toll-like Receptor 4. J Am Soc Nephrol. 2004;15(5):1289-99. PubMed PMID: 15100369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4. AU - Kato,Sawako, AU - Yuzawa,Yukio, AU - Tsuboi,Naotake, AU - Maruyama,Shoichi, AU - Morita,Yoshiki, AU - Matsuguchi,Tetsuya, AU - Matsuo,Seiichi, PY - 2004/4/22/pubmed PY - 2004/7/20/medline PY - 2004/4/22/entrez SP - 1289 EP - 99 JF - Journal of the American Society of Nephrology : JASN JO - J Am Soc Nephrol VL - 15 IS - 5 N2 - 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. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/15100369/Endotoxin_induced_chemokine_expression_in_murine_peritoneal_mesothelial_cells:_the_role_of_toll_like_receptor_4_ L2 - https://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=15100369 DB - PRIME DP - Unbound Medicine ER -