Metallothionein induction in cultured rat hepatocytes byarthritic rat serum, activated macrophages, IL-6 IL-11 and leukaemia inhibitory factor

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dc.contributor.authorCoyle, P.
dc.contributor.authorPhilcox, J.
dc.contributor.authorRofe, A.
dc.date.issued1995
dc.description.abstractPotential 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.identifier.citationInflammation Research, 1995; 44(11):475-481
dc.identifier.doi10.1007/BF01837913
dc.identifier.issn1023-3830
dc.identifier.issn1420-908X
dc.identifier.urihttp://hdl.handle.net/2440/5639
dc.language.isoen
dc.publisherBirkhauser Verlag
dc.source.urihttps://doi.org/10.1007/bf01837913
dc.subjectLiver
dc.subjectCells, Cultured
dc.subjectMacrophages
dc.subjectAnimals
dc.subjectRats
dc.subjectArthritis, Experimental
dc.subjectZinc
dc.subjectDexamethasone
dc.subjectLipopolysaccharides
dc.subjectGrowth Inhibitors
dc.subjectMetallothionein
dc.subjectInterleukin-6
dc.subjectInterleukin-11
dc.subjectLymphokines
dc.subjectMacrophage Activation
dc.subjectMale
dc.subjectLeukemia Inhibitory Factor
dc.titleMetallothionein induction in cultured rat hepatocytes byarthritic rat serum, activated macrophages, IL-6 IL-11 and leukaemia inhibitory factor
dc.typeJournal article
pubs.publication-statusPublished

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