IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway.
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.
Kroeger
Kelly M
KM
Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California, USA.
Sullivan
Brandon M
BM
Locksley
Richard M
RM
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018793:Interleukin-13 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology*; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D048308:Mitogen-Activated Protein Kinase 14 / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C506535:Il33 protein, mouse; D018793:Interleukin-13; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D015847:Interleukin-4; D051057:Proto-Oncogene Proteins c-akt; D048308:Mitogen-Activated Protein Kinase 14