Activin A stimulates type IV collagenase (matrix metalloproteinase-2) production in mouse peritoneal macrophages.
The role of activin, a dimer of inhibin beta subunit, in mouse peritoneal macrophages was evaluated. Activin activity in the cultured macrophages was augmented in response to activation by LPS. In Western blot analysis, immunoreactive activin A was detected in the culture medium only when the macrophages were stimulated by LPS. Although mRNA expression of betaA subunit was detected, that of alpha and betaB subunit was not found in macrophages by reverse RT-PCR. The activin betaA mRNA level was increased in macrophages by LPS, suggesting that the activin production augmented by LPS is regulated at the mRNA level of the betaA gene. The mRNAs of four activin receptors (ActRI, ActRIB, ActRII, and ActRIIB) were also detected in the peritoneal macrophages, and the mRNA levels, except for ActRIB, were decreased during the LPS treatment. Exogenous activin A stimulated the mRNA expression and gelatinolytic activity of matrix metalloproteinase-2 (MMP-2) in macrophages in both the presence and the absence of LPS. In contrast, activin did not affect the production of MMP-9 in macrophages. These results suggested that 1) mouse peritoneal macrophages produced activin A; 2) expression of activin A was enhanced with activation of the macrophages; 3) the macrophages also expressed activin receptors; and 4) exogenous activin A stimulated MMP-2 expression and activity, implicating activin A as an positive regulator of MMP-2 expression. Considering that MMP-2 constitutes the rate-limiting proteinase governing the degradation of basement membrane collagens, activin A may be involved in migration and infiltration of macrophages through the basement membrane in an inflammatory state.
Ogawa
K
K
Laboratory Animal Research Center, RIKEN, Wako, Saitama, Japan.
Funaba
M
M
Mathews
L S
LS
Mizutani
T
T
D029404:Activin Receptors; D028341:Activins; D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D007265:Inhibins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D020536:Enzyme Activators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors; D020778:Matrix Metalloproteinase 2