Though toll-like receptor 4 (TLR4) signaling is commonly referenced,131,132,133 CREB is a downstream mediator of TLR4 signaling,134 resulting in TNFα, IL-6, and COX-2 (cyclooxygenase-2) expression, and has been proposed and investigated in classical NEC pathogenesis. This evidence concerns the gene PTGS2 and necrotizing enterocolitis.