Role of reactive oxygen species in IL-1β-stimulated sustained ERK activation and MMP-9 induction

American Journal of Physiology - Heart and Circulatory Physiology - Tập 281 Số 6 - Trang H2568-H2574 - 2001
Milind V. Gurjar1, Jason DeLeon1, Ram V. Sharma1, Ramesh C. Bhalla1
11 Department of Anatomy and Cell Biology, The University of Iowa College of Medicine, Iowa City, Iowa 52242

Tóm tắt

We have recently demonstrated that interleukin-1β (IL-1β) stimulates matrix metalloproteinase-9 (MMP-9) induction. In this study we have investigated the roles of superoxide and extracellular signal-regulated kinase (ERK) activation in MMP-9 induction following exposure to IL-1β. IL-1β stimulated biphasic ERK activation in vascular smooth muscle (VSM) cells, a transient activation that reached a maximum at 15 min and declined to baseline levels within 1 h, and a second phase of sustained ERK activation lasting up to 8 h. To determine the role of ERK in IL-1β-stimulated MMP-9 induction, we treated cells with the specific ERK pathway inhibitor PD-98059 at different time intervals after IL-1β stimulation. Addition of PD-98059 up to 4 h after IL-1β stimulation significantly inhibited MMP-9 induction, suggesting a role for sustained ERK activation in MMP-9 induction. IL-1β treatment stimulated superoxide production in VSM cells that was inhibited by pretreatment of cells with the superoxide scavenger N-acetyl-l-cysteine (NAC) and also by overexpression of the human manganese superoxide dismutase (MnSOD) gene. Treatment of VSM cells with NAC selectively inhibited the sustained phase of ERK activation without influencing the transient phase, suggesting a role for reactive oxygen species in sustained ERK activation. In addition, both NAC treatment and MnSOD overexpression significantly inhibited IL-1β-stimulated MMP-9 induction ( P < 0.05). The results demonstrate that IL-1β-dependent MMP-9 induction is mediated by superoxide-stimulated ERK activation.

Từ khóa


Tài liệu tham khảo

10.1161/01.RES.77.1.29

10.1161/01.RES.75.3.539

10.1152/ajplung.1996.271.6.L932

10.1161/01.RES.85.6.524

10.1016/S0002-9378(00)70239-0

10.1161/01.RES.87.10.840

10.1016/S0008-6363(99)00175-3

10.1161/01.RES.77.5.863

10.1046/j.1523-1755.2000.00808.x

10.1161/01.ATV.16.8.1000

10.1161/01.CIR.97.24.2445

10.1172/JCI117619

10.1016/S0955-0674(99)80028-3

10.1016/0002-9343(94)90294-1

10.1161/01.RES.86.5.494

10.1016/S0022-2143(98)90019-1

10.1161/01.HYP.26.6.854

10.1161/01.ATV.19.12.2871

10.1152/jappl.2001.91.3.1380

10.1016/0014-5793(94)00754-3

10.1006/abio.1994.1186

10.1172/JCI117746

10.1172/JCI118949

10.1152/ajpheart.1992.263.1.H257

10.1161/01.RES.85.12.1179

10.1074/jbc.274.7.4347

10.1016/S0741-5214(98)70298-8

10.1172/JCI116491

10.1161/01.RES.81.6.904

10.1161/01.RES.70.3.593

10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4

10.1038/362801a0

10.1152/ajpheart.1999.276.5.H1450

10.1126/science.270.5234.296

10.1074/jbc.273.49.33027

10.1002/(SICI)1097-4652(199908)180:2<271::AID-JCP15>3.0.CO;2-D

Thông tin
Thông tin xuất bản

American Journal of Physiology - Heart and Circulatory Physiology

Tập 281 Số 6

H2568-H2574

Thông tin tác giả