p38 MAPK inhibition selectively mitigates inflammatory mediators and VEGF production in AF cells co-cultured with activated macrophage-like THP-1 cells

J. H. Kim, R. K. Studer, N. V. Vo, G. A. Sowa, J. D. Kang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objectives: Recent data have suggested that macrophages are involved in the pathogenesis of discogenic back pain and enhance the secretion of inflammatory mediators in co-cultured annulus fibrosus (AF) cells. The purpose of these studies is to determine the role of p38 mitogen-activated protein kinase (p38 MAPK) signaling in the interactions between macrophage and AF cells. Methods: Human AF cells were co-cultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells with and without p38 MAPK inhibition. Conditioned media from co-cultured cells were assayed for interleukin (IL)-6, IL-8, prostaglandin E2 (PGE2), PGF2α, and vascular endothelial growth factor (VEGF). Naïve and macrophage-exposed AF cell responses to 10 ng/ml tumor necrosis factor-α (TNF-α) were compared using the same outcome measures. Results: IL-6, IL-8, PGE2, PGF2α, and VEGF were secreted in greater quantities by cells maintained in co-culture compared to macrophages or AF cells cultured alone. SB202190 blunted IL-6, PGE2, and PGF2α production in a dose-dependent manner in co-culture. However, it did not suppress IL-8 and VEGF production. TNF-α-stimulated AF cell inflammatory mediators were up-regulated by macrophage exposure. SB202190 successfully suppressed IL-6, IL-8, PGE2, and PGF2α secretion in macrophage-exposed AF cells in response to TNF-α. Conclusions: Annular injury can result in macrophage infiltration, and this can cause enhanced inflammatory mediator and VEGF production by AF cells. The p38 MAPK pathway signals are responsible for much of IL-6 and PG secretion from AF cells with macrophage-like cells, suggesting that blockade of this signal may serve as a therapeutic approach to discogenic pain.

Original languageEnglish
Pages (from-to)1662-1669
Number of pages8
JournalOsteoarthritis and Cartilage
Volume17
Issue number12
DOIs
Publication statusPublished - 2009 Dec

Keywords

  • Annulus fibrosus
  • Low back pain
  • Macrophages
  • SB202190
  • p38 MAPK

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

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