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https://hdl.handle.net/2440/5639
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dc.contributor.author | Coyle, P. | - |
dc.contributor.author | Philcox, J. | - |
dc.contributor.author | Rofe, A. | - |
dc.date.issued | 1995 | - |
dc.identifier.citation | Inflammation Research, 1995; 44(11):475-481 | - |
dc.identifier.issn | 1023-3830 | - |
dc.identifier.issn | 1420-908X | - |
dc.identifier.uri | http://hdl.handle.net/2440/5639 | - |
dc.description.abstract | Potential mediators of hepatic metallothionein (MT) synthesis in adjuvant-induced arthritis were investigated in cultured rat hepatocytes. Sera from arthritic rats (14 d post-adjuvant treatment) in the presence of Zn (50 mumol/L)+dexamethasone (Dex; 1 mumol/L) increased metallothionein (MT) accumulation by 34% above that obtained with control rat serum with Zn+Dex. Endogenous IL-6 activity in serum from arthritic rats was 93 +/- 49 U/mL and was undetectable in control rat serum. The activities of TNF, IL-1 and corticosterone concentrations were the same in control and arthritic rats. The accumulation of MT in hepatocytes in the presence of Zn (10 mumol/L)+Dex (1 mumol/L) was enhanced 29% and 49% by media from lipopolysaccharide (LPS)-stimulated peritoneal macrophage (PMM) and Kupffer cell cultures (KCM), respectively. The response with PMM and KCM was quantitatively the same as that with interleukin-6 (IL-6). Analysis of PMM and KCM showed activities of 1,000-10,000 U/mL for IL-6, 100-1000 U/mL for TNF and < 10,000 U/mL for IL-1, the latter detected only in PMM. LPS alone enhanced the accumulation of MT above Zn+Dex in a dose dependent manner. A significant LPS response was obtained at 5 mg/L with a maximal stimulation above Zn+Dex of 38% at 10 mg/L. This direct stimulation of MT by LPS was not part of the response observed with PMM and KCM where the final LPS concentration in culture was only 0.1 mg/L. Other cytokines capable of synergy with Zn+Dex on MT synthesis were investigated. Interleukin-11 (IL-11) increased the Zn+Dex induction in a dose dependent manner with maximal stimulation at 100 U/mL of 40%. A small stimulation of 12% above Zn+Dex was obtained with leukaemia inhibitory factor (LIF) at concentrations greater than 100 U/mL. No enhancement of the Zn+Dex response was obtained with interleukin-3 (1000 U/mL), interleukin-4 (10 micrograms/L), platelet activating factor (5 nmol/L) or granulocyte-colony stimulating factor (5 micrograms/L). Neither IL-11 nor LIF enhanced the response obtained with Zn+Dex+IL-6. The results demonstrate that mediators present in arthritic rat serum and in LPS-stimulated PMM and KCM cause a quantitatively similar response on MT accumulation as IL-6. IL-11 and to a lesser extent LIF, are also potential mediators of MT synthesis in inflammation. | - |
dc.language.iso | en | - |
dc.publisher | Birkhauser Verlag | - |
dc.source.uri | http://dx.doi.org/10.1007/bf01837913 | - |
dc.subject | Liver | - |
dc.subject | Cells, Cultured | - |
dc.subject | Macrophages | - |
dc.subject | Animals | - |
dc.subject | Rats | - |
dc.subject | Arthritis, Experimental | - |
dc.subject | Zinc | - |
dc.subject | Dexamethasone | - |
dc.subject | Lipopolysaccharides | - |
dc.subject | Growth Inhibitors | - |
dc.subject | Metallothionein | - |
dc.subject | Interleukin-6 | - |
dc.subject | Interleukin-11 | - |
dc.subject | Lymphokines | - |
dc.subject | Macrophage Activation | - |
dc.subject | Male | - |
dc.subject | Leukemia Inhibitory Factor | - |
dc.title | Metallothionein induction in cultured rat hepatocytes byarthritic rat serum, activated macrophages, IL-6 IL-11 and leukaemia inhibitory factor | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1007/BF01837913 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest 5 Pathology publications |
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