Upon activation of the TNF-α pathway, it has been shown to either upregulate the transcription of Muc2 through the PI3K/AKT/NF-κB pathways or downregulate through the JNK pathway in the IBD model [109], In contrast to the above result, a number of large cross-sectional studies further suggest certain constraints between the signal pathways of NF-κB and JNK, leading to Muc2 transcription without any obvious influence by pro-inflammatory cytokines [109], including IL-1 and TNF-α, which has been found to stimulate the expression of MUC2 mRNA on the intestinal cancer cell line LS180 [110]. Here, TNF is linked to irritable bowel syndrome.