Changes in gene expression induced by histamine, fexofenadine and osthole: Expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1β in PBMC allergic and non-allergic patients

Immunobiology. 2017 Mar;222(3):571-581. doi: 10.1016/j.imbio.2016.11.004. Epub 2016 Nov 10.

Abstract

Introduction: Fexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1β and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion.

Objective: The purpose was to investigate expression pattern in asthma PBMC.

Methods: The cultures were treated 72h with FXF and osthole. We measured mRNA expression of histamine HRH-1, COX-2, NF-κB-p50, CCR1, IL-1β and CCL5/RANTES with Real-Time PCR (RT-PCR).

Results: The present study suggest that osthole may be a potential inhibitor of histamine H1 receptor activity. We also demonstrated that cells cultured with histamine increase COX-2 mRNA expression and osthole reduce it.

Conclusion: Allergy remains one of the most common chronic diseases in Europe and it is rapidly approaching epidemic proportions; with current predictions estimating that the number of allergy-afflicted will equal the healthy population by 2020. It is therefore paramount to find new pharmaceuticals which successfully combat allergic disease.

Keywords: Allergic disease; Antihistamine drugs; Cultures in vitro; Expression in PBMCs.

MeSH terms

  • Adult
  • Case-Control Studies
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Coumarins / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Female
  • Gene Expression Regulation / drug effects*
  • Histamine / pharmacology*
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / metabolism
  • Terfenadine / analogs & derivatives*
  • Terfenadine / pharmacology

Substances

  • Chemokine CCL5
  • Coumarins
  • Interleukin-1beta
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Histamine H1
  • Terfenadine
  • Histamine
  • fexofenadine
  • Cyclooxygenase 2
  • osthol