PURPOSE: Stromelysin-1 ( @entity1549 ) degrades extracellular matrix and increases aqueous outflow. In the trabecular meshwork (TM), @entity1192 is a potent inducer of @entity1549 expression. In different cells, @entity1192 activates different signaling pathways, such as nuclear factor (NF)-kappaB-mediated protein expression, the @entity3900 ( @entity3900 )-activated @entity3899 cascade, and activator protein (AP)-1-associated transcription. In the present study, pharmacological tools were used to delineate the signaling mechanism involved in the effect of @entity1192 on @entity1549 production in @entity1 TM cells compared with other ocular cells. METHODS: @entity1 TM and three other ocular cells (ciliary muscle, corneoscleral fibroblast, and lamina cribrosa) were cultured in 24-well plates in the presence or absence of @entity1192 , with or without specific inhibitors of selected signaling pathways. Secreted proMMP-3 was quantified by ELISA, and @entity1549 activity was assayed by casein zymography. RESULTS: @entity1192 (5 ng/mL) increased proMMP-3 levels in @entity1 TM cells to 10- to 38-fold of control (P < 0.001). The effect of @entity1192 was blocked by G  6976, a protein kinase C micro ( @entity6164 micro ) inhibitor; @entity4286 , a @entity8047 ( @entity8047 ) inhibitor; @entity4285 , a @entity1435 inhibitor; and @entity69922 , an AP-1 inhibitor; but not by inhibitors of casein kinase II, @entity2451 , @entity3900 , @entity16091 ( @entity16091 ), cyclooxygenases, lipoxygenase, or sphingomyelinase. @entity69922 did not inhibit the effect of @entity1192 on @entity1549 production in the other ocular cells tested. CONCLUSIONS: Based on the pharmacological effects of the inhibitors, the data indicate that activation of @entity6164 micro, @entity8047 , and @entity1435 leading to the activation of AP-1 is critical to the @entity1192 -stimulated upregulation of @entity1549 in @entity1 TM cells. Therefore, it is likely that compounds that activate the AP-1 pathway would upregulate the production of @entity1549 and improve aqueous outflow.

Involvement of AP-1 in interleukin-1alpha-stimulated XXXX expression in @entity1 trabecular meshwork cells.

@entity1 :: ('9606', 'Species') :: ['human', 'Human'] @entity8047 :: ('5609', 'Gene') :: ['mitogen-activated protein kinase kinase', 'MEK'] @entity2451 :: ('4790', 'Gene') :: ['NFkappaB'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity69922 :: ('MESH:C106195', 'Chemical') :: ['SR11302'] @entity1549 :: ('4314', 'Gene') :: ['MMP-3'] @entity16091 :: ('2822', 'Gene') :: ['phospholipase D', 'PLD'] @entity3900 :: ('151056', 'Gene') :: ['PLA(2)', 'phospholipase A(2)'] @entity1192 :: ('3552', 'Gene') :: ['interleukin (IL)-1alpha', 'IL-1alpha'] @entity3899 :: ('CHEBI:32395', 'Chemical') :: ['arachidonate'] @entity6164 :: ('MESH:C566847', 'Disease') :: ['PKC'] @entity4285 :: ('MESH:C090942', 'Chemical') :: ['SB202190'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059']
@entity1549 :: (4314,Gene) :: ['MMP-3']
