The extracellular matrix protein matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal

Objective and design This prospective experimental study aims to investigate whether matrilin-2 is released from burn injury and induces post-burn inflammatory responses as an endogenous danger signal. Subjects Fifteen burn patients, 15 volunteers, 12 matrilin-2-deficient mice, 36 C57BL/6 mice and raw 264.7 cells. Methods Matrilin-2 levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction. The inflammatory cytokines production in Matn2 deficient mice and wide type mice were detected by ELISA. Macrophages were activated by recombinant mouse MATN2 with or without adding anti-Toll-like receptor (TLR) 4 antibody. Student's t test and one-way analysis of variance were used for statistical analysis. Results The matrilin-2 levels in serum of burned patients were drastically elevated as compared to those of healthy controls. The matrilin-2 levels in burned mice were significantly increased than those of non-burned controls, whereas the matrilin-2 mRNA expression was not significantly changed after burn. In addition, Matn2 deficient mice showed remarkably less inflammatory cytokines production and less neutrophil infiltration in lung. Exogenous MATN2 induced potent expression of proinflammatory cytokines production in macrophages, which was inhibited by anti-TLR4 antibody. Conclusion Matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal, partly through a TLR4-mediated mechanism.