The contact of human macrophages with extracellular matrix proteins selectively induces expression of proinflammatory cytokines.
The interaction of macrophages with proteins of the extracellular matrix (ECM) is important for the regulation of the immune and nonimmune functions displayed by these cells. Little, however, is known about the ability of different ECM proteins to transmit inflammatory signals into macrophages. Here we investigated the effect of the ECM proteins collagen type I, fibrin and fibronectin on the expression of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-8 using RT-PCR, Northern and Western blot analysis and ELISA technique. It was found that collagen strongly induced IL-1beta and IL-8 expression in the macrophages. Fibronectin also stimulated cytokine expression, however, the amounts of the specific mRNAs were significantly lower compared to those induced by collagen. On the protein level IL-1beta revealed a close correlation to the mRNA expression. In contrast, fibrin did not elicit any IL-1beta and IL-8 response. These data show that different ECM proteins vary in their ability to induce proinflammatory cytokine expression in human macrophages suggesting that the protein composition of the ECM might be crucial in the initiation of inflammatory processes.
Schiffer
R
R
Interdisciplinary Centre of Clinical Research 'Biomat', Medical Faculty, RWTH Aachen, Germany. rschiffer@post.klinikum.rwth-aachen.de
Klein
B
B
Klosterhalfen
B
B
Zwadlo-Klarwasser
G
G
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005337:Fibrin / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D005337:Fibrin; D003094:Collagen