H2R deficiency activated the IL1 signaling pathway. (A) Western blot of HDNs and LDNs treated with LPS using antibodies against p-iκBa, p-ERK, total ERK, p-p38, total p38, adenosine 3′,5′-cyclic monophosphate–dependent protein kinase (PKA) substrate, and γ-actin. (B) The cytokine production of WT and H2R KO HDNs treated with LPS by MagPix (n = 3). (C) IL1β production in WT and H2R KO LDNs treated with LPS (100 ng/mL) by MagPix (n = 3). (D and E) Immunofluorescence staining of S100A8 and IL1β for (D) inflammation and for (E) inflammation-associated colon tumors (magnification: 40× and 400×). (F) The expression levels of Il1r1 in the colon tumors of ApcMin/+ and ApcMin/+; H2R KO mice by qRT-PCR (n = 4). Means ± SD are shown. ∗P < .05. (G) The association between IL1R1 expression in cancers and overall survival in CRC patients through the R2 database. Ctrl, control; DAPI, 4′,6-diamidino-2-phenylindole; GM-CSF, Granulocyte macrophage-colony stimulating factor; IFN, interferon.