Inflammation by activated macrophage-like THP-1 cells increases human dura mater cell adhesion with alteration of integrin (21) and matrix metalloproteinase

Abstract

This study was designed to investigate (i) extracellular matrix to specify adhesive substrates to human dura mater cell (hDMC); (ii) the alteration on adhesion-related molecules in hDMC; and (iii) secreted matrix metalloproteinases (MMPs) linked with extracellular matrix remodeling after exposure to inflammation. The hDMC was cultured from human dura mater tissue, and the studies were performed with hDMC after co-culturing with macrophage like THP-1 cells (M phi). The adhesion of co-cultured hDMC through collagen I increased 6.4-fold and through collagen IV increased 5.0-fold compared with the adhesion of naive cells (p<0.001). Integrin subtype (21) expression was increased 6.3-fold (p<0.001) and (1) expression was decreased 2.0-fold (p<0.001) in the co-cultured cells compared with the naive cells. Co-culturing induced significant increases in MMP-1 (13.9-fold, p<0.01), MMP-3 (7.6-fold, p<0.01), and VEGF (VEGF: 3.8-fold, p<0.05) expression and decreases in MMP-9 (0.1-fold, p<0.01) compared with the sum of naive hDMC and M phi values. Increased hDMC adhesion under inflammatory conditions is caused by an increased cellular affinity for collagen I and IV mediated by increased hDMC levels of integrin subtype (21) and environmental MMP-1, -3 and decreased MMP-9. Selective integrin subtype (21) inhibition assay showed 37.8% and 35.7% reduction in adhesion of co-cultured hDMC to collagen I (p<0.001) and IV (p=0.057), respectively. The present study provides insight into the pathological conditions related to dura mater adhesion in inflammation. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2019.