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Levosimendan inhibits interleukin-1β-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts.
Eur J Pharmacol. 2013 Oct 15; 718(1-3):332-9.EJ

Abstract

Cell migration and matrix metalloproteinases (MMPs) secretion in cardiac fibroblasts are important processes in the cardiac remodeling during the development of cardiac diseases and are regulated by proinflammatory cytokines. Although levosimendan, a novel inotropic agent, is expected to have some beneficial influences on preventing cardiac remodeling, its effects on proinflammatory cytokines-induced functional changes in cardiac fibroblasts have not been clarified. Therefore, we investigated the effects of levosimendan on interleukin (IL)-1β-induced MMP-9 secretion and migration in adult rat cardiac fibroblasts. Primary cardiac fibroblasts were isolated from adult male Wistar rats. MMP-9 secretion in culture medium and extracellular signal-regulated kinase (ERK) phosphorylation in cell lysate were measured by using Western blotting. Gelatin zymography was performed to measure activity of secreted MMP-9. MMP-9 mRNA expression in the cell was measured by using reverse transcription polymerase chain reaction. Boyden chamber assay was performed for detection of migration. Levosimendan (3-100 μM) concentration-dependently inhibited IL-1β (4 ng/ml)-induced MMP-9 secretion, activity and mRNA expression. Levosimendan inhibited IL-1β (4 ng/ml)-induced ERK phosphorylation. Levosimendan (10 and 100 μM) inhibited IL-1β-induced migration, and CTTHWGFTLC peptide (10 μM), an MMP inhibitor, or PD98059 (50 μM), an ERK inhibitor, also suppressed it. The present study for the first time demonstrated in adult rat cardiac fibroblasts that levosimendan inhibits IL-1β-induced migration at least partly through the inhibition of MMP-9 secretion via suppressing ERK phosphorylation.

Authors+Show Affiliations

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, Japan. Electronic address: mokada@vmas.kitasato-u.ac.jp.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24012928

Citation

Okada, Muneyoshi, et al. "Levosimendan Inhibits Interleukin-1β-induced Cell Migration and MMP-9 Secretion in Rat Cardiac Fibroblasts." European Journal of Pharmacology, vol. 718, no. 1-3, 2013, pp. 332-9.
Okada M, Suzuki A, Yamawaki H, et al. Levosimendan inhibits interleukin-1β-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. Eur J Pharmacol. 2013;718(1-3):332-9.
Okada, M., Suzuki, A., Yamawaki, H., & Hara, Y. (2013). Levosimendan inhibits interleukin-1β-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. European Journal of Pharmacology, 718(1-3), 332-9. https://doi.org/10.1016/j.ejphar.2013.08.013
Okada M, et al. Levosimendan Inhibits Interleukin-1β-induced Cell Migration and MMP-9 Secretion in Rat Cardiac Fibroblasts. Eur J Pharmacol. 2013 Oct 15;718(1-3):332-9. PubMed PMID: 24012928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levosimendan inhibits interleukin-1β-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. AU - Okada,Muneyoshi, AU - Suzuki,Atsushi, AU - Yamawaki,Hideyuki, AU - Hara,Yukio, Y1 - 2013/09/03/ PY - 2013/02/12/received PY - 2013/06/28/revised PY - 2013/08/24/accepted PY - 2013/9/10/entrez PY - 2013/9/10/pubmed PY - 2014/6/11/medline KW - Cardiac fibroblasts KW - Interleukin-1β KW - Levosimendan KW - Matrix metalloproteinase-9 KW - Migration SP - 332 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 718 IS - 1-3 N2 - Cell migration and matrix metalloproteinases (MMPs) secretion in cardiac fibroblasts are important processes in the cardiac remodeling during the development of cardiac diseases and are regulated by proinflammatory cytokines. Although levosimendan, a novel inotropic agent, is expected to have some beneficial influences on preventing cardiac remodeling, its effects on proinflammatory cytokines-induced functional changes in cardiac fibroblasts have not been clarified. Therefore, we investigated the effects of levosimendan on interleukin (IL)-1β-induced MMP-9 secretion and migration in adult rat cardiac fibroblasts. Primary cardiac fibroblasts were isolated from adult male Wistar rats. MMP-9 secretion in culture medium and extracellular signal-regulated kinase (ERK) phosphorylation in cell lysate were measured by using Western blotting. Gelatin zymography was performed to measure activity of secreted MMP-9. MMP-9 mRNA expression in the cell was measured by using reverse transcription polymerase chain reaction. Boyden chamber assay was performed for detection of migration. Levosimendan (3-100 μM) concentration-dependently inhibited IL-1β (4 ng/ml)-induced MMP-9 secretion, activity and mRNA expression. Levosimendan inhibited IL-1β (4 ng/ml)-induced ERK phosphorylation. Levosimendan (10 and 100 μM) inhibited IL-1β-induced migration, and CTTHWGFTLC peptide (10 μM), an MMP inhibitor, or PD98059 (50 μM), an ERK inhibitor, also suppressed it. The present study for the first time demonstrated in adult rat cardiac fibroblasts that levosimendan inhibits IL-1β-induced migration at least partly through the inhibition of MMP-9 secretion via suppressing ERK phosphorylation. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/24012928/Levosimendan_inhibits_interleukin_1β_induced_cell_migration_and_MMP_9_secretion_in_rat_cardiac_fibroblasts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(13)00603-1 DB - PRIME DP - Unbound Medicine ER -