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* Department of Biology and
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23284;
Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030;
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23284; and
¶ Department of Infectious Diseases, St. Jude Childrens Research Hospital, Memphis, TN 38105
Mast cells are known for their roles in allergy, asthma, systemic anaphylaxis, and inflammatory disease. IL-10 can regulate inflammatory responses and may serve as a natural regulator of mast cell function. We examined the effects of IL-10 on in vitro-cultured mouse and human mast cells, and evaluated the effects of IL-10 on Fc
RI in vivo using mouse models. IgE receptor signaling events were also assessed in the presence or absence of IL-10. IL-10 inhibited mouse mast cell Fc
RI expression in vitro through a Stat3-dependent process. This down-regulation was consistent in mice tested in vivo, and also on cultured human mast cells. IL-10 diminished expression of the signaling molecules Syk, Fyn, Akt, and Stat5, which could explain its ability to inhibit IgE-mediated activation. Studies of passive systemic anaphylaxis in IL-10-transgenic mice showed that IL-10 overexpression reduced the IgE-mediated anaphylactic response. These data suggest an important regulatory role for IL-10 in dampening mast cell Fc
RI expression and function. IL-10 may hence serve as a mediator of mast cell homeostasis, preventing excessive activation and the development of chronic inflammation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health (1R01 AI59638) and The Jeffress Trust Foundation (J-833) (to J.J.R.).
2 Address correspondence and reprint requests to Dr. John J. Ryan, Biology Department, Virginia Commonwealth University, Box 842012, Richmond, VA 23284-2012. E-mail address: jjryan{at}vcu.edu
3 Abbreviations used in this paper: Tg, transgenic; BMMC, bone marrow-derived mast cell; SCF, stem cell factor; NFDM, nonfat dry milk; PSA, passive systemic anaphylaxis; cRPMI, complete RPMI.
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