IL-33 can promote survival, adhesion and cytokine production in human mast cells.
IL-33 is a recently identified member of the IL-1 family of molecules, which also includes IL-1 and IL-18. IL-33 binds to the receptor, T1/ST2/IL-1R4, and can promote cytokine secretion by Th2 cells and NF-kappaB phosphorylation in mouse mast cells. However, the effects of these molecules, especially IL-33, in human mast cells are poorly understood. Expression of the receptors for IL-1 family molecules, specifically, IL-1R1, IL-18R and T1/ST2, was detectable intracellularly in human umbilical cord blood-derived mast cells (HUCBMCs) by flow cytometry, but was scarcely detectable on the cells' surface. However, IL-1beta, IL-18 or IL-33 induced phosphorylation of Erk, p38 and JNK in naïve HUCBMCs, and IL-33 or IL-1beta, but not IL-18, enhanced the survival of naive HUCBMCs and promoted their adhesion to fibronectin. IL-33 or IL-1beta also induced IL-8 and IL-13 production in naïve HUCBMCs, and enhanced production of these cytokines in IgE/anti-IgE-stimulated HUCBMCs, without enhancing secretion of either PGD(2) or histamine. Moreover, IL-33-mediated IL-8 production by HUCBMCs was markedly reduced by the p38 MAPK inhibitor, SB203580. In contrast to findings with mouse mast cells, IL-18 neither induced nor enhanced secretion of the mediators PGD(2) or histamine by HUCBMCs. Our findings identify previously unknown functions of IL-33 in human mast cells. One of these is that IL-33, like IL-1beta, can induce cytokine production in human mast cells even in the absence of stimuli of FcepsilonRI aggregation. Our findings thus support the hypothesis that IL-33 may enhance mast cell function in allergic disorders and other settings, either in the presence or absence of co-stimulation of mast cells via IgE/antigen-FcepsilonRI signals.
Iikura
Motoyasu
M
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Suto
Hajime
H
Kajiwara
Naoki
N
Oboki
Keisuke
K
Ohno
Tatsukuni
T
Okayama
Yoshimichi
Y
Saito
Hirohisa
H
Galli
Stephen J
SJ
Nakae
Susumu
S
D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005353:Fibronectins / Q000502:physiology*; D006636:Histamine Release / Q000502:physiology; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D020382:Interleukin-18 / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism
D005353:Fibronectins; C506536:IL33 protein, human; D018793:Interleukin-13; D020382:Interleukin-18; D053583:Interleukin-1beta; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D017472:Receptors, Interleukin-1; D020928:Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2