IL‐3 is an important differentiation factor for the development of prostaglandin E2‐producing macrophages between C57BL/6 and BALB/c mice

AbstractWe have previously reported that peritoneal and splenic macrophages from Th2‐dominant BALB/c mice produced higher amounts of prostaglandin (PG) E2 than cells from C57BL/6 mice. In this study, we investigated how macrophages from BALB/c mice acquire the ability of enhanced PGE2 production, using bone marrow‐derived macrophages differentiated by M‐CSF, GM‐CSF or IL‐3. There is no strain difference in PGE2 production by GM‐CSF‐ and M‐CSF‐differentiated macrophages; however, IL‐3‐differentiated macrophages from BALB/c mice produced higher amounts of PGE2 and lower amounts of type I cytokines than cells from C57BL/6 mice. IL‐3‐differentiated macrophages from BALB/c mice expressed larger amounts of mRNA of membrane‐bound (microsomal) PGE synthase‐1 (mPGES‐1). The amounts of PGE2 produced by macrophages were significantly reduced in mPGES‐1‐deficient mice, and these mice displayed enhanced Th1 responses after Propionibacterium acnes treatment compared with wild‐type mice. Microarray analysis revealed 63 genes that are differentially expressed more than fivefold in macrophages between C57BL/6 and BALB/c mice. These results indicate that mPGES‐1‐mediated PGE2 produced by macrophages regulates immune responses, and IL‐3 is an important factor for the differentiation of macrophages that produce higher amounts of PGE2 through mPGES‐1 activity in BALB/c mice.