BACKGROUND: The histamine H4 receptor (H4R) is a novel therapeutic target to treat allergic inflammation. OBJECTIVE: To profile messenger RNA (mRNA) expression of H₄R isoforms in human cells and evaluate the effects of atopy and grass pollen season on H₄R expression in peripheral blood leukocytes ex vivo. METHODS: H₄R isoform expression was assayed by quantitative polymerase chain reaction in human airway and peripheral RNA. During low and high grass pollen seasons, leukocytes were isolated from venous blood and fractionated into peripheral blood mononuclear cells and polymorphonuclear cells (PMN). H₄R expression was determined and related to atopy, defined by a level of specific IgE to Timothy grass pollen of ≥0.35 kU(A)/L (n = 7 atopic patients and 9 controls). RESULTS: Expression of total and full length H₄R was at the limit of detection but predominant in peripheral blood leukocytes, where truncated H₄R was expressed exclusively (≤300-fold less). Suggestive evidence for total H₄R in airway cells and brain indicated an expression ≤260-fold lower than in peripheral blood mononuclear cells. Total H₄R mRNA expression was unaffected by atopy or grass pollen season, but truncated H₄R was significantly reduced during high grass pollen season in total leukocytes, independently of atopy (P < .01). CONCLUSION: H₄R mRNA is predominantly expressed in peripheral blood leukocytes, and total H₄R expression levels are unrelated to atopy or grass pollen season. Atopy-independent seasonal variation in truncated H₄R expression might affect putative negative regulation of full length H4R during high grass pollen season. If verified, this should be considered during the design of drugs targeting H₄R to treat allergic inflammation, particularly for seasonal allergic rhinitis.
BACKGROUND: The histamine H4 receptor (H4R) is a novel therapeutic target to treat allergic inflammation. OBJECTIVE: To profile messenger RNA (mRNA) expression of H₄R isoforms in human cells and evaluate the effects of atopy and grass pollen season on H₄R expression in peripheral blood leukocytes ex vivo. METHODS: H₄R isoform expression was assayed by quantitative polymerase chain reaction in human airway and peripheral RNA. During low and high grass pollen seasons, leukocytes were isolated from venous blood and fractionated into peripheral blood mononuclear cells and polymorphonuclear cells (PMN). H₄R expression was determined and related to atopy, defined by a level of specific IgE to Timothy grass pollen of ≥0.35 kU(A)/L (n = 7 atopic patients and 9 controls). RESULTS: Expression of total and full length H₄R was at the limit of detection but predominant in peripheral blood leukocytes, where truncated H₄R was expressed exclusively (≤300-fold less). Suggestive evidence for total H₄R in airway cells and brain indicated an expression ≤260-fold lower than in peripheral blood mononuclear cells. Total H₄R mRNA expression was unaffected by atopy or grass pollen season, but truncated H₄R was significantly reduced during high grass pollen season in total leukocytes, independently of atopy (P < .01). CONCLUSION: H₄R mRNA is predominantly expressed in peripheral blood leukocytes, and total H₄R expression levels are unrelated to atopy or grass pollen season. Atopy-independent seasonal variation in truncated H₄R expression might affect putative negative regulation of full length H4R during high grass pollen season. If verified, this should be considered during the design of drugs targeting H₄R to treat allergic inflammation, particularly for seasonal allergic rhinitis.
Authors: Pertti Panula; Paul L Chazot; Marlon Cowart; Ralf Gutzmer; Rob Leurs; Wai L S Liu; Holger Stark; Robin L Thurmond; Helmut L Haas Journal: Pharmacol Rev Date: 2015-07 Impact factor: 25.468
Authors: Mariángeles Clauzure; Mónica A Táquez Delgado; Jude M Phillip; Maria V Revuelta; Leandro Cerchietti; Vanina A Medina Journal: Int J Mol Sci Date: 2022-01-26 Impact factor: 5.923