In activated mast cells, IL-1 up-regulates the production of several Th2-related cytokines including IL-9.
Mast cells can play detrimental roles in the pathophysiology and mortality observed in anaphylaxis and other Th2-dominated allergic diseases. In contrast, these cells contribute to protective host defense mechanisms against parasitic worm infections. After IgE/Ag activation, mast cells can produce multiple cytokines that may enhance allergic inflammations, while a similar panel of Th2-related cytokines may support immunological strategies against parasites. Here we report that in primary mouse bone marrow-derived mast cells activated by ionomycin or IgE/Ag, the proinflammatory mediator IL-1 (alpha or beta) up-regulated production of IL-3, IL-5, IL-6, and IL-9 as well as TNF, i.e., cytokines implicated in many inflammatory processes including those associated with allergies and helminthic infections. IL-1 did not induce significant cytokine release in the absence of ionomycin or IgE/Ag, suggesting that Ca-dependent signaling was required. IL-1-mediated enhancement of cytokine expression was confirmed at the mRNA level by Northern blot and/or RT-PCR analysis. Our study reveals a role for IL-1 in the up-regulation of multiple mast cell-derived cytokines. Moreover, we identify mast cells as a novel source of IL-9. These results are of particular importance in the light of recent reports that strongly support a central role of IL-9 in allergic lung inflammation and in host defense against worm infections.
Hültner
L
L
GSF-National Research Center for Environment and Health, Institute of Experimental Hematology, München, Germany. hueltner@gsf.de
Kölsch
S
S
Stassen
M
M
Kaspers
U
U
Kremer
J P
JP
Mailhammer
R
R
Moeller
J
J
Broszeit
H
H
Schmitt
E
E
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004140:Dinitrophenols / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007073:Immunoglobulin E / Q000502:physiology; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D012710:Serum Albumin, Bovine / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004140:Dinitrophenols; D007375:Interleukin-1; D016906:Interleukin-9; D012333:RNA, Messenger; C034638:dinitrophenyl-bovine serum albumin; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D015759:Ionomycin