TNF and colitis: In addition to the alkaline ceramidases, loss of Asah2, another ceramidase, has been shown to augment the elevation of many ceramide species and aggravate mouse colitis by upregulating Tnf-α and cyclooxygenase-2 expression in colon.25 These results together suggest that ceramidases have a key role in preventing hyper-activation of the immune response to the gut microbiota by maintaining the homeostasis of pro-inflammatory ceramides.