title: IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.
abstract: Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa.
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Baumann
authors.affiliation: Clinic for Visceral Surgery, Katharinenhospital, Stuttgart, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Feilhauer
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany. Electronic address: Lorentz@uni-hohenheim.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Lorentz
mesh_terms: D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D057906:Circadian Clocks / Q000187:drug effects* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D056926:CLOCK Proteins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Allergy; Circadian clock; Eosinophils; Mast cells