Inhibition of COX-2 modulates multiple functional pathways during acute inflammation and pain

Inhibition of COX-2 modulates multiple functional pathways during acute inflammation and pain. Theoretical schematic diagram depicts the genes and their pathway modulated by rofecoxib treatment during acute inflammation. Besides inhibiting COX-2 activity, rofecoxib may also produce its anti-inflammatory effect through (1) up-regulating annexins and SOD2 expression, which directly suppress the activity of phospholipase A2; (2) up-regulating SOCS3, which inhibit cytokine signaling by negative feedback regulation of JAK/STAT cascade; (3) down-regulation of the gene expression IL1 and C3. However, by shunting down the cyclooxygenase pathway and reducing COX-2-derived PGs production, rofecoxib may induce the over-expression of the pro-inflammatory mediators (4) leukotrienes (indicated by the thicker solid lines), and (5) IL6 and CCL2 (MCP-1). The latter may play a critical role in the development of the adverse effects attributed to COX-2 inhibitors. The solid lines indicate facilitation and the dashed lines indicate inhibition.

Publication

Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. () Xiao-Min Wang, et al. Pain. ;128(1-2):136-147. Figure: F5. Homo sapiens

Disease mentions