Interleukin-6 production by peritoneal mesothelial cells and its regulation by inflammatory factors in rats administered carbon tetrachloride intraperitoneally
- Department of Hygienic Chemistry, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543 (Japan)
We previously reported that a high level of interleukin-6 (IL-6), which is protective against CCl{sub 4}-induced hepatotoxicity, is produced in the peritoneal cavity in the early period after ip carbon tetrachloride (CCl{sub 4}) administration. The objective of this study was to identify the tissues and cells involved in IL-6 production and clarify the mechanisms underlying its regulation. IL-6 mRNA levels increased significantly in the serous membranes of the mesentery and peritoneum, but not in the parenchymal organs including liver, kidney and spleen, 3 h after ip CCl{sub 4} administration. Peritoneal mesothelial cells (PMCs), a major cell population in serous membranes, were isolated from rat peritoneal walls by trypsin digestion and cultured with peritoneal exudate fluid (PEF) from CCl{sub 4}-administered rats. PMCs produced a high level of IL-6 in the presence of PEF recovered 0.5 h after ip CCl{sub 4} administration. Analyses of PEF revealed that the levels of prostaglandin E{sub 2} (PGE{sub 2}), histamine, IL-1{alpha}, IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) increased immediately after ip CCl{sub 4} administration. These inflammatory factors, except for histamine, stimulated IL-6 production to varying degrees, in the following order: IL-1{alpha} > IL-1{beta} > TNF-{alpha} >> PGE{sub 2}. In summary, the present study indicates that the high level of IL-6 observed in the rat peritoneal cavity after ip CCl{sub 4} administration is at least partially produced by PMCs stimulated cooperatively with IL-1{alpha}, IL-1{beta}, TNF-{alpha} and PGE{sub 2}. These inflammatory factors may be released from tissues or cells either stimulated or injured directly by CCl{sub 4}.
- OSTI ID:
- 21077885
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 226, Issue 1; Other Information: DOI: 10.1016/j.taap.2007.08.014; PII: S0041-008X(07)00376-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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