Histamine H(1)- and H(4)-receptor expression in human colon-derived cell lines

In previous studies, we demonstrated the involvement of H(4)R in inflammatory bowel disease (IBD) and IBD-associated colon cancer in mice and could ascribe H(4)R-mediated histamine function to colon epithelial cells. The transferability of obtained data to humans is however lacking. Functional expression of H(4)R on colon epithelial cells is a prerequisite to pursue the hypothesis of involvement of H(4)R in carcinogenesis. Thus, we here compared the expression of histamine receptor subtypes in a series of cell lines. Out of these, three colon-derived cell lines displaying different combinations of H(1)R and H(4)R expression were submitted to functional analyses. Human hematopoietic HMC-1, HL-60, and U937, lung-derived A549 and Calu-3, and colorectal LoVo, SW 480, Caco-2, HT-29, and HCT116 cells were included in the study. mRNA expression was quantified by RT-qPCR. For functional analyses, Caco-2, HT-29, and HCT116 cells were treated by incubation with 1 – 10 µM histamine in the presence or absence of selective histamine receptor antagonists. Calcium mobilization, cAMP accumulation, and cell proliferation were measured by fluorimetry, mass spectrometry, and real-time bioimpedance measurements, respectively. Histamine receptor expression was heterogeneous in the cell lines tested. In most cell lines, we detected H(1)R mRNA while H(4)R mRNAs were found only occasionally. The colon-derived epithelial cell lines LoVo, SW480, and HT-29 expressed H(1)R mRNA exclusively, while in HCT116 cells H(1)R and H(4)R mRNAs and in CaCo-2 H(2)R mRNA were detectable. Subsequent functional analyses in HT29, Caco-2, and HCT116 cells, however, indicated that only HT-29 responded to histamine stimulation, by means of H(1)R. For a detailed analysis of histamine receptor function, esp. that of H(1)R and H(4)R, in human colon-derived cell lines, the cell lines tested here are not fully convenient unless genetically modified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00210-023-02565-8.