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PMID: 19451398 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway.

Journal of leukocyte biology ·Vol. 86 ·No. 4 ·2009-10-00 ·Pages 769-78

Kroeger KM, Sullivan BM, Locksley RM

Abstract

IL-4 and IL-13 are instrumental in the development and progression of allergy and atopic disease. Basophils represent a key source of these cytokines and produce IL-4 and IL-13 when stimulated with IL-18, a member of the IL-1 family of cytokines. Comparative analyses of the effects of caspase-1-dependent IL-1 family cytokines on basophil IL-4 and IL-13 production have not been performed, and the signaling pathway proteins required for FcepsilonRI-independent Th2 cytokine production from basophils remain incompletely defined. Using mouse bone marrow-derived cultured basophils, we found that IL-4 and IL-13 are produced in response to IL-18 or IL-33 stimulation. IL-18- or IL-33-mediated Th2 cytokine production is dependent on MyD88 and p38alpha signaling proteins. In addition, basophil survival increased in the presence of IL-18 or IL-33 as a result of increased Akt activation. Studies in vivo confirmed the potency of IL-18 and IL-33 in activating cytokine release from mouse basophils.

MeSH Terms
Animals Basophils/cytology,immunology Cell Survival/drug effects,immunology Cells, Cultured Female Interleukin-13/immunology Interleukin-18/immunology,pharmacology Interleukin-33 Interleukin-4/immunology Interleukins/immunology,pharmacology Mice Mice, Inbred BALB C Mice, Knockout Mitogen-Activated Protein Kinase 14/immunology Myeloid Differentiation Factor 88/immunology Proto-Oncogene Proteins c-akt/immunology Signal Transduction/drug effects,immunology Th2 Cells/immunology
Chemicals
Il33 protein, mouse Interleukin-13 Interleukin-18 Interleukin-33 Interleukins Myd88 protein, mouse Myeloid Differentiation Factor 88 Interleukin-4 Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinase 14
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kroeger Kelly M
Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California, USA.
Sullivan Brandon M
Locksley Richard M
References (35)
35 references, click to expand
  1. Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein.
    Mol Cell Biol. 1999 Nov;19(11):7519-28 PMID: 10523640
  2. Serine phosphorylation of STATs.
    Oncogene. 2000 May 15;19(21):2628-37 PMID: 10851062
  3. IL-33 can promote survival, adhesion and cytokine production in human mast cells.
    Lab Invest. 2007 Oct;87(10):971-8 PMID: 17700564
  4. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.
    Am J Respir Crit Care Med. 2001 Jul 15;164(2):277-81 PMID: 11463601
  5. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma.
    J Immunol. 2000 Mar 1;164(5):2701-10 PMID: 10679111
  6. Cloning of a new cytokine that induces IFN-gamma production by T cells.
    Nature. 1995 Nov 2;378(6552):88-91 PMID: 7477296
  7. Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma.
    Blood. 2006 Oct 1;108(7):2290-9 PMID: 16794249
  8. Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants.
    J Leukoc Biol. 1998 Jun;63(6):650-7 PMID: 9620655
  9. Basophils and type 2 immunity.
    Curr Opin Hematol. 2008 Jan;15(1):59-63 PMID: 18043247
  10. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
    Immunity. 1998 Jul;9(1):143-50 PMID: 9697844
  11. Airway hyperresponsiveness: a story of mice and men and cytokines.
    Clin Rev Allergy Immunol. 2003 Feb;24(1):85-110 PMID: 12644720
  12. Differences in signaling pathways by IL-1beta and IL-18.
    Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8815-20 PMID: 15161979
  13. A two-step process for cytokine production revealed by IL-4 dual-reporter mice.
    Immunity. 2005 Oct;23(4):419-29 PMID: 16226507
  14. Surface membrane antigen alteration on blood basophils in patients with Hymenoptera venom allergy under immunotherapy.
    J Allergy Clin Immunol. 2000 Dec;106(6):1190-5 PMID: 11112905
  15. Differential role for mitogen-activated protein kinases in IgE-dependent signaling in human peripheral blood basophils: in contrast to p38 MAPK, c-Jun N-terminal kinase is poorly expressed and does not appear to control mediator release.
    Int Arch Allergy Immunol. 2005 Apr;136(4):329-39 PMID: 15741731
  16. Molecular cloning and characterization of the human AKT1 promoter uncovers its up-regulation by the Src/Stat3 pathway.
    J Biol Chem. 2005 Nov 25;280(47):38932-41 PMID: 16174774
  17. Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production.
    Immunity. 2004 Mar;20(3):267-77 PMID: 15030771
  18. Biologic basis for interleukin-1 in disease.
    Blood. 1996 Mar 15;87(6):2095-147 PMID: 8630372
  19. IL-18 activates STAT3 in the natural killer cell line 92, augments cytotoxic activity, and mediates IFN-gamma production by the stress kinase p38 and by the extracellular regulated kinases p44erk-1 and p42erk-21.
    J Immunol. 2000 Aug 1;165(3):1307-13 PMID: 10903731
  20. Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production.
    J Immunol. 2005 Jan 15;174(2):1063-72 PMID: 15634931
  21. Interleukin 3-dependent survival by the Akt protein kinase.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11345-50 PMID: 9326612
  22. IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13962-6 PMID: 10570181
  23. Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/akt: involvement of MEK upstream of Bad phosphorylation.
    Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7439-44 PMID: 9636168
  24. Role of cytokines in allergic airway inflammation.
    Int Arch Allergy Immunol. 2007;142(4):265-73 PMID: 17124428
  25. Up-regulation of IL-18 in allergic rhinitis.
    Allergy. 2002 Sep;57(9):825-30 PMID: 12169180
  26. Interleukin-1/Toll receptor family members: receptor structure and signal transduction pathways.
    J Interferon Cytokine Res. 2000 Oct;20(10):843-55 PMID: 11054272
  27. Interleukin-13 induction of 15-lipoxygenase gene expression requires p38 mitogen-activated protein kinase-mediated serine 727 phosphorylation of Stat1 and Stat3.
    Mol Cell Biol. 2003 Jun;23(11):3918-28 PMID: 12748293
  28. IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals.
    J Leukoc Biol. 2007 Dec;82(6):1481-90 PMID: 17881510
  29. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation.
    J Immunol. 1999 Apr 15;162(8):4472-81 PMID: 10201984
  30. Interleukin-18 regulates both Th1 and Th2 responses.
    Annu Rev Immunol. 2001;19:423-74 PMID: 11244043
  31. Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases.
    Nat Immunol. 2005 Apr;6(4):390-5 PMID: 15735648
  32. Regulation of mediator secretion in human basophils by p38 mitogen-activated protein kinase: phosphorylation is sensitive to the effects of phosphatidylinositol 3-kinase inhibitors and calcium mobilization.
    J Leukoc Biol. 2002 Aug;72(2):391-400 PMID: 12149431
  33. Expression and function of the ST2 gene in a murine model of allergic airway inflammation.
    Clin Exp Allergy. 2002 Oct;32(10):1520-6 PMID: 12372135
  34. Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways.
    Am J Respir Crit Care Med. 1999 Sep;160(3):873-8 PMID: 10471611
  35. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.
    Immunity. 2005 Nov;23(5):479-90 PMID: 16286016
Article Info
Journal
Journal of leukocyte biology
Abbr.
J Leukoc Biol
ISSN
1938-3673
Published
2009-10-00
Epub
2009-00-18
Pages
769-78
Language
English
Region
United States
NLM ID
8405628
PMCID
PMC2752018
Subset
IM
Grants
NIAID NIH HHS · R01 AI026918 · United States
NIAID NIH HHS · R37 AI026918 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · AI026918 · United States
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