Molecular and biochemical pharmacology of the histamine H4 receptor.
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ABSTRACT:
SUBMITTER: Leurs R
PROVIDER: S-EPMC2697796 | biostudies-literature | 2009 May
REPOSITORIES: biostudies-literature
Publications
Molecular and biochemical pharmacology of the histamine H4 receptor.
Leurs Rob R Chazot Paul L PL Shenton Fiona C FC Lim Herman D HD de Esch Iwan J P IJ
British journal of pharmacology 20090501 1
The elucidation of the human genome has had a major impact on histamine receptor research. The identification of the human H4 receptor by several groups has been instrumental for a new appreciation of the role of histamine in the modulation of immune function. In this review, we summarize the historical developments and the molecular and biochemical pharmacology of the H4 receptor. ...[more]
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Project description:BackgroundAlthough the role of histamine H4 receptor (H4R) in immune cells is being extensively investigated, its immunomodulatory function in cancer is completely unknown. This study aimed to investigate the role of H4R in antitumour immunity in a model of triple-negative breast cancer.MethodsWe evaluated growth parameters, histological characteristics and the composition of tumour, splenic and tumour draining lymph node (TDLN) immune subsets, in a syngeneic model, developed orthotopically with 4T1 cells in H4R knockout (H4R-KO) and wild-type mice.ResultsMice lacking H4R show reduced tumour size and weight, decreased number of lung metastases and percentage of CD4+ tumour-infiltrating T cells, while exhibiting increased infiltration of NK cells and CD19+ lymphocytes. Likewise, TDLN of H4R-KO mice show decreased CD4+ T cells and T regulatory cells (CD4+CD25+FoxP3+), and increased percentages of NK cells. Finally, H4R-deficient mice show decreased Tregs in spleens and non-draining lymph nodes, and a negative correlation between tumour weight and the percentages of CD4+, CD19+ and NK splenic cells, suggesting that H4R also regulates antitumour immunity at a systemic level.ConclusionsThis is the first report that demonstrates the participation of H4R in antitumour immunity, suggesting that H4R could be a target for cancer treatment.
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Project description:BackgroundThe immune system is likely involved in the pathophysiology of Meniere's disease (MD). However, its role of patients with MD has not been well studied. Given that histamine H4 receptors are highly expressed in immune system, we tested the hypothesis that histamine H4 receptor gene polymorphisms are a potential contributor to the risk of MD.MethodsA group of patients was enrolled with a diagnosis of definite MD based on the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines and a control group of patients without any vestibular disease. We selected one SNP, rs77485247 in HRH4 and conducted an exploratory investigation of its correlations with the symptoms of vertigo and proinflammatory cytokines levels in MD patients.ResultsHRH4 rs77485247 polymorphism may be associated with the risk of MD. Furthermore, basal levels of proinflammatory cytokines, such as IL-1β and TNF-α, in PBMCs are increased in patients with MD compared to control patients. This increased basal level of proinflammatory cytokines is prominent in MD patients with the A allele.ConclusionsThese suggested that HRH4 rs77485247 polymorphism may be an important mediator in regulating proinflammatory cytokines, which are involved in the pathogenesis of MD.
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