Native and fragmented fibronectin oppositely modulate ... - CiteSeerX

Uncorrected Version. Published on February 27, 2007 as DOI:10.1189/jlb.0506328

Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9 Barak Marom,*,†,1 Michal A. Rahat,*,1,2 Nitza Lahat,* Lea Weiss-Cerem,† Amalia Kinarty,* and Haim Bitterman† *Immunology Research Unit and †Ischemia-Shock Research Laboratory, Carmel Medical Center, Rappaport Family Institute for Research in the Medical Sciences, and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Abstract: Monocytes remodel the extracellular matrix (ECM) by secreting proteins composing the ECM such as fibronectin (FN) and degrading proteases such as matrix metalloproteinase-9 (MMP9), which cleaves FN into fragments. The effects of FN and its fragmented products on the expression of monocyte MMP-9 are controversial and largely unknown. We showed that in human monocytes, the proinflammatory cytokine TNF-␣ induced MMP-9 secretion and increased fragmentation of FN into distinct fragments. When primary monocytes or the U937 monocytic cell line were incubated on a plastic substrate, plastic-coated with native FN, and plastic-coated with fragmented FN (frag-FN), native FN inhibited TNF-␣-induced proMMP-9 secretion by twofold (P