Abstract
PURPOSE. To examine the effect of medroxyprogesterone 17- acetate (MPA) on interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts. METHODS. Rabbit corneal fibroblasts were cultured in threedimensional collagen gels with or without MPA. Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression or activity of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) was evaluated by immunoblot analysis or gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. RESULTS. MPA inhibited IL-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. MMP expression and activation as well as TIMP expression in corneal fibroblasts exposed to IL-1β were also inhibited by MPA. MPA had no effect on cell proliferation or viability. MPA inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK. IL- 1β-induced MMP expression and activation as well as collagen degradation were also blocked by the p38 MAPK inhibitor SB203580. CONCLUSIONS. MPA inhibited MMP expression and thereby suppressed collagen degradation by corneal fibroblasts induced by IL-1β. Furthermore, inhibition of p38 MAPK phosphorylation by MPA may contribute to its inhibition of collagen degradation.
| Original language | English |
|---|---|
| Pages (from-to) | 4213-4219 |
| Number of pages | 7 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 53 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jun 1 2012 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
Cite this
Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts. / Zhou, Hongyan; Kimura, Kazuhiro; Orita, Tomoko; Nishida, Teruo; Sonoda, Koh Hei.
In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 7, 01.06.2012, p. 4213-4219.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts
AU - Zhou, Hongyan
AU - Kimura, Kazuhiro
AU - Orita, Tomoko
AU - Nishida, Teruo
AU - Sonoda, Koh Hei
PY - 2012/6/1
Y1 - 2012/6/1
N2 - PURPOSE. To examine the effect of medroxyprogesterone 17- acetate (MPA) on interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts. METHODS. Rabbit corneal fibroblasts were cultured in threedimensional collagen gels with or without MPA. Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression or activity of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) was evaluated by immunoblot analysis or gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. RESULTS. MPA inhibited IL-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. MMP expression and activation as well as TIMP expression in corneal fibroblasts exposed to IL-1β were also inhibited by MPA. MPA had no effect on cell proliferation or viability. MPA inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK. IL- 1β-induced MMP expression and activation as well as collagen degradation were also blocked by the p38 MAPK inhibitor SB203580. CONCLUSIONS. MPA inhibited MMP expression and thereby suppressed collagen degradation by corneal fibroblasts induced by IL-1β. Furthermore, inhibition of p38 MAPK phosphorylation by MPA may contribute to its inhibition of collagen degradation.
AB - PURPOSE. To examine the effect of medroxyprogesterone 17- acetate (MPA) on interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts. METHODS. Rabbit corneal fibroblasts were cultured in threedimensional collagen gels with or without MPA. Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression or activity of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) was evaluated by immunoblot analysis or gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. RESULTS. MPA inhibited IL-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. MMP expression and activation as well as TIMP expression in corneal fibroblasts exposed to IL-1β were also inhibited by MPA. MPA had no effect on cell proliferation or viability. MPA inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK. IL- 1β-induced MMP expression and activation as well as collagen degradation were also blocked by the p38 MAPK inhibitor SB203580. CONCLUSIONS. MPA inhibited MMP expression and thereby suppressed collagen degradation by corneal fibroblasts induced by IL-1β. Furthermore, inhibition of p38 MAPK phosphorylation by MPA may contribute to its inhibition of collagen degradation.
UR - http://www.scopus.com/inward/record.url?scp=84866285574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866285574&partnerID=8YFLogxK
U2 - 10.1167/iovs.11-8822
DO - 10.1167/iovs.11-8822
M3 - Article
C2 - 22577074
AN - SCOPUS:84866285574
VL - 53
SP - 4213
EP - 4219
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 7
ER -