Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells.
Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated. A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.
Kumon
Y
Y
Second Department of Internal Medicine, Kochi Medical School, Kohasu Okoh-Cho, Nankoku, Kochi, Japan. kumony@kochi-ms.ac.jp
Suehiro
T
T
Hashimoto
K
K
Sipe
J D
JD
D000210:Acute-Phase Reaction / Q000235:genetics; D000328:Adult; D000450:Aldosterone / Q000494:pharmacology; D001011:Aorta / Q000166:cytology*; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C083772:SAA2 protein, human; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D000450:Aldosterone; D003907:Dexamethasone; D003345:Corticosterone; D006854:Hydrocortisone