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

verfasst von

Jasper Carsten Schrammel, Martin König, Miriam Frommer, Kaya Saskia Andersen, Marla Kirsten, Roland Seifert, Detlef Neumann, Bastian Schirmer

Abstract

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.

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)

Typ

Artikel

Journal

Naunyn-Schmiedeberg's Archives of Pharmacology

Band

396

Seiten

3683-3693

Anzahl der Seiten

11

ISSN

0028-1298

Publikationsdatum

10.07.2023

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Pharmakologie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1007/s00210-023-02565-8 (Zugang: Offen)