2023 Volume 57 Issue 1 Pages 55-62
Although the complement cascade is the basis of innate immunity, little is known about its mechanism. NGF acts as an important mediator of the cascade acting downstream of the C5a receptor 1 (C5aR1). Although NGF is known to be involved in inflammatory pain, the mechanism by which NGF causes pain remains unclear. It is known that an injection of Complement 5a (C5a) into the hind paw skin of mice elicits painful behavior and enhances NGF expression in dermal macrophages. Sorting Nexin25 (SNX25) is part of a family of proteins that play important roles in membrane trafficking, intracellular signaling, membrane remodeling, and organelle motility, some of which also contribute to the immune system. Using the macrophage cell-line, J774.1, we examined whether SNX25 is involved in C5a-induced NGF expression at the cellular level. Treatment of J774.1 with C5a enhanced NGF and SNX25 expression. Western blotting revealed that C5a-induced NGF expression was reduced by Snx25 siRNA. Snx25+/- mice had lower NGF levels and showed a pain-insensitive phenotype in response to C5a. We propose that the expression level of C5a-induced NGF is controlled by macrophages through SNX25 signaling. (J Osaka Dent Univ 2023; 57: 55-62)
