Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209
Abstract
Having demonstrated recently that hydrocortisone (HC) suppresses
intranuclear and total cellular nuclear factor-B (NF-
B) and
increases inhibitor
B (I
B) 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.
MMPs 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.