Assessment of the mechanism that leads to the upregulation of this enzyme in macrophages demonstrated that immune complexes, a central part of rheumatic diseases, via the Fc receptors activate ERK1/2, which phosphorylates the transcription factor p-ELK1 (Figure 5), in turn upregulating 15-PGDH expression by binding to Ets-binding sites on the gene promotor (42). This evidence concerns the gene MAPK3 and rheumatic disorder.