The expression of COX 2, which is, in contrast to that of NOS 2, upregulated due to the AOM/DSS treatment, strictly depends on the presence of the H4R. Thus, H4R signaling in epithelial cells may induce COX 2 expression [42], leading to an increased production of PGE2, which, subsequently, induces the production of CXCL1 [43] and CXCL2, resulting in tumor progression. Here, CXCL1 is linked to neoplasm.