TY - JOUR
T1 - IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock
AU - Baumann, Anja
AU - Feilhauer, Katharina
AU - Bischoff, Stephan C.
AU - Froy, Oren
AU - Lorentz, Axel
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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 4. h around the circadian cycle by FcεRI 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.
AB - 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 4. h around the circadian cycle by FcεRI 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.
KW - Allergy
KW - Circadian clock
KW - Eosinophils
KW - Mast cells
UR - http://www.scopus.com/inward/record.url?scp=84920097627&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2014.10.026
DO - 10.1016/j.molimm.2014.10.026
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C2 - 25466613
AN - SCOPUS:84920097627
SN - 0161-5890
VL - 64
SP - 76
EP - 81
JO - Molecular Immunology
JF - Molecular Immunology
IS - 1
ER -