Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK

Jalahalli M. Siddesha, Anthony J. Valente, Siva S.V.P. Sakamuri, Jason D. Gardner, Patrice Delafontaine, Makoto Noda, Bysani Chandrasekar

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H2O2 generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H2O2 generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. J. Cell. Physiol. 229: 845-855, 2014.

Original languageEnglish (US)
Pages (from-to)845-855
Number of pages11
JournalJournal of Cellular Physiology
Volume229
Issue number7
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Siddesha, J. M., Valente, A. J., Sakamuri, S. S. V. P., Gardner, J. D., Delafontaine, P., Noda, M., & Chandrasekar, B. (2014). Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK. Journal of Cellular Physiology, 229(7), 845-855. https://doi.org/10.1002/jcp.24511