TY - JOUR
T1 - Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9)
AU - Aljada, A.
AU - Ghanim, H.
AU - Mohanty, P.
AU - Hofmeyer, D.
AU - Tripathy, D.
AU - Dandona, P.
PY - 2001
Y1 - 2001
N2 - Having demonstrated recently that hydrocortisone (HC) suppresses intranuclear and total cellular nuclear factor-κB (NF-κB) and increases inhibitor κB (IκB) in mononuclear cells (MNC), in vivo, we have now investigated the effect of hydrocortisone on the other major pro-inflammatory transcription factor, AP-1 and the two proteins, MMP-2 and MMP-9, whose transcription is modulated by it. MMP's hydrolyze extracellular matrix proteins and thus, allow the spread of inflammation. HC (100 mg) was given intravenously to eight normal subjects following an overnight fast. Blood samples were obtained at 0, 1, 2, 4, 8 and 24 h. MNC were separated and the nuclear fractions and cellular homogenates were prepared by standard techniques. AP-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). Plasma MMP-2 and MMP-9 were measured by ELISA. AP-1 binding activity fell significantly at 1, 2, 4 and 8 h. Plasma MMP-2 concentration also decreased significantly at 1, 2, 4 and 8 h while MMP-9 decreased at 1 and 2 h. These data demonstrate that the acute anti-inflammatory effect of HC, in vivo, is, in part, due to AP-1 suppression and a reduction in MMP-2 and MMP-9. Thus, HC may reduce the extracellular spread of inflammation through the inhibition of matrix metalloproteinases.
AB - Having demonstrated recently that hydrocortisone (HC) suppresses intranuclear and total cellular nuclear factor-κB (NF-κB) and increases inhibitor κB (IκB) in mononuclear cells (MNC), in vivo, we have now investigated the effect of hydrocortisone on the other major pro-inflammatory transcription factor, AP-1 and the two proteins, MMP-2 and MMP-9, whose transcription is modulated by it. MMP's hydrolyze extracellular matrix proteins and thus, allow the spread of inflammation. HC (100 mg) was given intravenously to eight normal subjects following an overnight fast. Blood samples were obtained at 0, 1, 2, 4, 8 and 24 h. MNC were separated and the nuclear fractions and cellular homogenates were prepared by standard techniques. AP-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). Plasma MMP-2 and MMP-9 were measured by ELISA. AP-1 binding activity fell significantly at 1, 2, 4 and 8 h. Plasma MMP-2 concentration also decreased significantly at 1, 2, 4 and 8 h while MMP-9 decreased at 1 and 2 h. These data demonstrate that the acute anti-inflammatory effect of HC, in vivo, is, in part, due to AP-1 suppression and a reduction in MMP-2 and MMP-9. Thus, HC may reduce the extracellular spread of inflammation through the inhibition of matrix metalloproteinases.
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U2 - 10.1210/jc.86.12.5988
DO - 10.1210/jc.86.12.5988
M3 - Article
C2 - 11739475
AN - SCOPUS:0035216954
SN - 0021-972X
VL - 86
SP - 5988
EP - 5991
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -