Cheung, BMY

Li, CYY

Tang, F

Wong, LYF

Hong Kong Medical Journal

HKU Scholars Hub

Title The Cytokine response of rat macrophages tolipopolysaccharide is modulated by adrenomedullinAuthor(s) Cheung, BMY; Wong, LYF; Li, CYY; Tang, FCitationThe 8th Medical Research Conference Abstracts, Hong KongMedical Journal, Hong Kong, China, 25-26 January 2003, v. 9 n. 1Supp 1, p. 26Issued Date 2003URL http://hdl.handle.net/10722/46924Rights Creative Commons: Attribution 3.0 Hong Kong License26      HKMJ Vol 9 No 1 February 2003 SupplementIncreased adrenomedullin expression in the heart, the lung and the mesentericartery by endotoxinY.Y.Li, F.Tang1 and B.M.Y. Cheung2Departments of Physiology1 and Medicine 2, Faculty of MedicineThe University of Hong KongPrevious studies have shown that the circulating levels of adrenomedullin (AM) are elevated during inflammation.The levels of AM and its messenger RNA (mRNA) in various tissues during the time course of inflammationremain to be determined. To study this, inflammation was induced in rats by intraperitoneal injection of lipopoly-saccharide (LPS, 10mg/kg). The tissues were harvested at 0, 1, 3 and 6 hours after LPS administration. Tissue levelsof AM were determined by radioimmunoassay. The gene expression levels of AM were determined by solutionhybridization-RNase protection assay of preproAM mRNA levels. The preproAM mRNA levels were increased inmesenteric artery and right atrium at 1 hour after LPS injection, in the left ventricle and the lung at 3 and 6 hoursafter LPS injection and in the right ventricle at 6 hours after LPS injection. These results suggest that AM synthesisincreases in these tissues by LPS at the time intervals specified. In addition, AM contents increased in the lung at 3and 6 hours after LPS injection. From these data and the mRNA result, it is concluded that there is an increase inAM release in the lung. As the plasma AM levels were elevated at 3 and 6 hours, the results show that the lung maybe an important organ for AM secretion in the septic state. However, the AM levels in the mesenteric artery wereincreased at 1, 3 and 6 hours whereas the preproAM mRNA were only elevated at 1 hour after LPS injection. Theresults would indicate an increase in AM release only at 1 hour after LPS injection and a decrease in AM release at3 and 6 hours. The responses of the lung and the mesenteric artery in terms of AM secretion are different.Acknowledgement: RGC grant.The Cytokine response of rat macrophages to lipopolysaccharide is modulated byadrenomedullinBMY Cheung, LYF Wong, CYY Li,* F Tang*Department of Medicine & *Department of Physiology, University of Hong KongIntroduction: Adrenomedullin (AM) is now recognised to be involved in inflammation. We investigated whetherAM is an inflammatory or anti-inflammatory cytokine.Method: Rat macrophages (NR8383) were incubated at 106 cells/well in 3.5-cm tissue culture plates in RPMI 1640medium containing 1% fetal bovine serum in the absence or presence of 10ng/mL to 1µg/mL AM. Conditionedmedia of parallel cultures were removed at 0, 3, 6, and 24-hours after AM stimulation. Secretion of cytokinesincluding TNF-α and IL-6 were measured using ELISA. To test whether AM is anti-inflammatory, macrophageswere activated by 1ng/mL to 1µg/mL lipopolysaccharide (LPS) in the absence or presence of 1_g/ml AM. Thecytokine response was measured in the conditioned media at 0, 3, 6, and 24-hours.Results: Basal secretion of TNF-α and IL-6 were 29.2±2.0 pg/mL and 58.7±2.8 pg/mL respectively. AM increasedTNF-α concentration by 115.4±41.4% but reduced IL-6 concentration by 56.3±4.9 % at 24 hours. LPS at 1 ng/mLenhanced TNF-α by 45-fold and IL-6 production by 11-fold. The presence of AM reduced the TNF-α and IL-6response to 66% and 49% respectively.Conclusion: Our results suggest that AM modulates cytokine secretion from rat macrophages and may thus have aregulatory role in inflammation.CVS-15CVS-16

The Cytokine response of rat macrophages to lipopolysaccharide is modulated by adrenomedullin

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The Cytokine response of rat macrophages to lipopolysaccharide is modulated by adrenomedullin

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