Induction of metalloelastase mRNA in murine peritoneal macrophages by diethylmaleate.
Macrophage-specific metalloelastase (MME) hydrolyzes elastin and other matrix proteins and plays an important physiological role in tissue remodeling and pathological tissue destruction. We have examined the effects of diethylmaleate (DEM), an electrophilic agent that reacts with sulfhydryls, on the expression of MME mRNA in mouse peritoneal macrophages. Quantification of MME mRNA by Northern blot analysis revealed that basal mRNA levels were quite low in freshly isolated cells, although mRNA levels increased markedly and reached a steady level within 12 h when cells were cultured in a serum-supplemented RPMI 1640 medium. When macrophages were challenged with DEM at 0.05-1.0 mM for 8 h the expression of the MME gene was enhanced further. In the presence of 0.1 mM DEM, the level of the MME mRNA increased 2-fold compared to the control levels after 6-9 h and decreased to control levels in 24 h. Other electrophilic agents, catechol and 1-chloro-2,4-dinitrobenzene, also enhanced MME gene expression. However, oxidative stress agents such as hydrogen peroxide, menadione, paraquat (an O-2 generator), sodium arsenite and cadmium chloride had no effect on MME gene expression. These results indicate that the electrophilic agents selectively enhance the expression of MME mRNA during primary culture of the macrophages.
Kawane
T
T
Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan.
Hou
J Q
JQ
Sato
H
H
Sugita
Y
Y
Bannai
S
S
Ishii
T
T
D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D008298:Maleates / Q000494:pharmacology*; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis*
D018076:DNA, Complementary; D008298:Maleates; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12; C014476:diethyl maleate