Histamine H₁- and H₄-receptor expression in human colon-derived cell lines

In previous studies, we demonstrated the involvement of H₄R in inflammatory bowel disease (IBD) and IBD-associated colon cancer in mice and could ascribe H₄R-mediated histamine function to colon epithelial cells. The transferability of obtained data to humans is however lacking. Functional expression of H₄R on colon epithelial cells is a prerequisite to pursue the hypothesis of involvement of H₄R 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 H₁R and H₄R 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 H₁R mRNA while H₄R mRNAs were found only occasionally. The colon-derived epithelial cell lines LoVo, SW480, and HT-29 expressed H₁R mRNA exclusively, while in HCT116 cells H₁R and H₄R mRNAs and in CaCo-2 H₂R 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 H₁R. For a detailed analysis of histamine receptor function, esp. that of H₁R and H₄R, in human colon-derived cell lines, the cell lines tested here are not fully convenient unless genetically modified.