IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Mast cell and basophil activation contributes to inflammation, bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-independent stimulation.
Because the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied the effects of IL-33 on these pathways. The IL-33- and SCF-stimulated HMC-1 cells were co-cultured with human lung fibroblasts and airway smooth muscle cells in a collagen gel contraction assay. IL-33 effects on IgE-mediated activation were studied in primary mast cells and basophils.
IL-33 synergized with adenosine, C5a, SCF, and NGF receptor activation. IL-33-stimulated and SCF-stimulated HMC-1 cells demonstrated enhanced collagen gel contraction when cultured with fibroblasts or smooth muscle cells. IL-33 also synergized with IgE receptor activation of primary human mast cells and basophils.
- Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. 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;23:479–90. CrossRef
- Smithgall MD, Comeau MR, Park Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol 2008;20:1019–30.
- Suzukawa M, Iikura M, Koketsu R, Nagase H, Tamura C, Komiya A, et al. An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor. J Immunol. 2008;181:5981–9.
- Pecaric-Petkovic T, Didichenko SA, Kaempfer S, Spiegl N, Dahinden CA. Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood. 2009;113:1526–34. CrossRef
- Suzukawa M, Koketsu R, Iikura M, Nakae S, Matsumoto K, Nagase H, et al. Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils. Lab Invest. 2008;88:1245–53. CrossRef
- Iikura M, Suto H, Kajiwara N, Oboki K, Ohno T, Okayama Y, et al. IL-33 can promote survival, adhesion and cytokine production in human mast cells. Lab Invest. 2007;87:971–8. CrossRef
- Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007;37:2779–86. CrossRef
- Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. The ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol. 2007;179:2051–4.
- Hudson CA, Christophi GP, Gruber RC, Wilmore JR, Lawrence DA, Massa PT. Induction of IL-33 expression and activity in central nervous system glia. J Leukoc Biol. 2008;84:631–43. CrossRef
- Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie ANJ, Lee RT. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007;117:1538–49. CrossRef
- Funakoshi-Tago M, Tago K, Hayakawa M, Tominaga S, Ohshio T, Sonoda Y, et al. TRAF6 is a critical signal transducer in IL-33 signaling pathway. Cell Signal. 2008;20:1679–86. CrossRef
- Ali S, Huber M, Kollewe C, Bischoff SC, Falk W, Martin MU. IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc Natl Acad Sci USA. 2007;104:18660–5. CrossRef
- Chackerian AA, Oldham ER, Murphy EE, Schmitz J, Pflanz S, Kastelein RA. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol. 2007;179:2551–5.
- Leung BP, Xu D, Culshaw S, McInnes LB, Liew FY. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol. 2004;173:145–50.
- Townsend MJ, Fallon PG, Matthews DJ, Jolin HE, McKenzie AN. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J Exp Med. 2000;191:1069–76. CrossRef
- Coyle AJ, Lloyd C, Tian J, Nguyen T, Erikkson C, Wang L, et al. Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med. 1999;190:895–902. CrossRef
- Lohning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos JC, et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA. 1998;95:6930–5. CrossRef
- Kearley J, Buckland KF, Mathie SA, Lloyd CM. Resolution of allergic inflammation and AHR is dependent upon disruption of the T1/ST2-IL-33 pathway. Am J Respir Crit Care Med 2009;179:772–81.
- Kurowska-Stolarska M, Kewin P, Murphy G, Russo RC, Stolarski B, Garcia CC, et al. IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol. 2008;181:4780–90.
- Hayakawa H, Hayakawa M, Kume A, Tominaga S. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem. 2007;282:26369–80. CrossRef
- Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK. IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol. 2008;180:2443–9.
- Amatucci A, Novobrantseva T, Gilbride K, Brickelmaier M, Hochman P, Ibraghimov A. Recombinant ST2 boosts hepatic Th2 response in vivo. J Leukoc Biol. 2007;82:124–32. CrossRef
- Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Morimoto M, Hayashi N, et al. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol. 2008;20:791–800. CrossRef
- Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, et al. IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci USA. 2008;105:10913–8. CrossRef
- Ho LH, Ohno T, Oboki K, Kajiwara N, Suto H, Iikura M, et al. IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals. J Leukoc Biol. 2007;82:1481–90. CrossRef
- Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol. 2007;179:2051–4.
- Ahamed J, Venkatesha RT, Thangam EB, Ali H. C3a enhances nerve growth factor-induced NFAT activation and chemokine production in a human mast cell line, HMC-1. J Immunol. 2004;172:6961–8.
- Bartosz G, Konig J, Keppler D, Hagmann W. Human mast cells secreting leukotriene C4 express the MRP1 gene-encoded conjugate export pump. Biol Chem. 1998;379:1121–6. CrossRef
- Min YD, Choi CH, Bark H, Son HY, Park HH, Lee S, et al. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-kappaB and p38 MAPK in HMC-1 human mast cell line. Inflamm Res. 2007;56:210–5. CrossRef
- Wong CK, Tsang CM, Ip WK, Lam CW. Molecular mechanisms for the release of chemokines from human leukemic mast cell line (HMC)-1 cells activated by SCF and TNF-alpha: roles of ERK, p38 MAPK, and NF-kappaB. Allergy. 2006;61:289–97. CrossRef
- Jensen BM, Metcalfe DD, Gilfillan AM. Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. Inflamm Allergy Drug Targets. 2007;6:57–62. CrossRef
- Huszar E, Vass G, Vizi E, Csoma Z, Barat E, Molnar Vilagos G, et al. Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Euro Respir J. 2002;20:1393–8 (see comment). CrossRef
- Ali H, Ahamed J, Hernandez-Munain C, Baron JL, Krangel MS, Patel DD. Chemokine production by G protein-coupled receptor activation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT. J Immunol. 2000;165:7215–23.
- Feoktistov I, Goldstein AE, Biaggioni I. Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase kinase in adenosine A2B receptor-mediated interleukin-8 production in human mast cells. Mol Pharmacol. 1999;55:726–34.
- Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I. Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. Circ Res. 2003;92:485–92. CrossRef
- Ryzhov S, Goldstein AE, Biaggioni I, Feoktistov I. Cross-talk between G(s)- and G(q)-coupled pathways in regulation of interleukin-4 by A(2B) adenosine receptors in human mast cells. Mol Pharmacol. 2006;70:727–35. CrossRef
- Ryzhov S, Goldstein AE, Matafonov A, Zeng D, Biaggioni I, Feoktistov I. Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: an A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. J Immunol. 2004;172:7726–33.
- Abe M, Hama H, Shirakusa T, Iwasaki A, Ono N, Kimura N, et al. Contribution of anaphylatoxins to allergic inflammation in human lungs. Microbiol Immunol. 2005;49:981–6.
- DiScipio RG, Schraufstatter IU. The role of the complement anaphylatoxins in the recruitment of eosinophils. Int Immunopharmacol. 2007;7:1909–23. CrossRef
- Werfel T, Oppermann M, Butterfield JH, Begemann G, Elsner J, Gotze O, et al. The human mast cell line HMC-1 expresses C5a receptors and responds to C5a but not to C5a(desArg). Scand J Immunol. 1996;44:30–6. CrossRef
- Margulis A, Nocka KH, Wood NL, Wolf SF, Goldman SJ, Kasaian MT. MMP dependence of fibroblast contraction and collagen production induced by human mast cell activation in a three-dimensional collagen lattice. Am J Physiol Lung Cell Mol Physiol. 2009;296:L236–47. CrossRef
- Bergers G, Reikerstorfer A, Braselmann S, Graninger P, Busslinger M. Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. Embo J. 1994;13:1176–88.
- Wojta J, Kaun C, Zorn G, Ghannadan M, Hauswirth AW, Sperr WR, et al. C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils. Blood. 2002;100:517–23. CrossRef
- Nilsson G, Johnell M, Hammer CH, Tiffany HL, Nilsson K, Metcalfe DD, et al. C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway. J Immunol. 1996;157:1693–8.
- Tsukamoto H, Irie A, Nishimura Y. B-Raf contributes to sustained extracellular signal-regulated kinase activation associated with interleukin-2 production stimulated through the T cell receptor. J Biol Chem. 2004;279:48457–65. CrossRef
- Tu VC, Sun H, Bowden GT, Chen QM. Involvement of oxidants and AP-1 in angiotensin II-activated NFAT3 transcription factor. Am J Physiol Cell Physiol. 2007;292:C1248–55. CrossRef
- Yang TT, Xiong Q, Graef IA, Crabtree GR, Chow CW. Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. Mol Cell Biol. 2005;25:907–20. CrossRef
- Margulis A, Nocka KH, Brennan AM, Deng B, Fleming M, Goldman SJ, et al. Mast cell-dependent contraction of human airway smooth muscle cell-containing collagen gels: influence of cytokines, matrix metalloproteases, and serine proteases. J Immunol. 2009;183:1739–50. CrossRef
- Kasaian MT, Clay MJ, Happ MP, Garman RD, Hirani S, Luqman M. IL-4 production by allergen-stimulated primary cultures: identification of basophils as the major IL-4-producing cell type. Int Immunol. 1996;8:1287–97. CrossRef
- Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7:827–40. CrossRef
- Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38. CrossRef
- Palmer G, Lipsky BP, Smithgall MD, Meininger D, Siu S, Talabot-Ayer D, et al. The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33. Cytokine. 2008;42:358–64. CrossRef
- Ali M, Zhang G, Thomas WR, McLean CJ, Bizzintino JA, Laing IA, et al. Investigations into the role of ST2 in acute asthma in children. Tissue Antigens. 2009;73:206–12. CrossRef
- Oshikawa K, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Ohno S, et al. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med. 2001;164:277–81.
- Hayakawa H, Hayakawa M, Kume A, Tominaga SI. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem 2007;282(36):26369-80.
- Bulek K, Swaidani S, Qin J, Lu Y, Gulen MF, Herjan T, et al. The essential role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulation of Th2 immune response. J Immunol. 2009;182:2601–9. CrossRef
- Bree A, Schlerman FJ, Wadanoli M, Tchistiakova L, Marquette K, Tan XY, et al. IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J Aller Clin Immunol. 2007;119:1251–7. CrossRef
- Kasaian MT, Donaldson DD, Tchistiakova L, Marquette K, Tan XY, Ahmed A, et al. Efficacy of IL-13 neutralization in a sheep model of experimental asthma. Am J Respir Cell Mol Biol. 2007;36:368–76. CrossRef
- Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Tertilt C, Bopp T, et al. Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines. J Immunol. 2006;177:6667–74.
- Monticelli S, Solymar DC, Rao A. Role of NFAT proteins in IL13 gene transcription in mast cells. J Biol Chem. 2004;279:36210–8. CrossRef
- Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest. 1993;92:1736–44. CrossRef
- Yamamoto T, Hartmann K, Eckes B, Krieg T. Role of stem cell factor and monocyte chemoattractant protein-1 in the interaction between fibroblasts and mast cells in fibrosis. J Dermatol Sci. 2001;26:106–11. CrossRef
- Baghestanian M, Hofbauer R, Kiener HP, Bankl HC, Wimazal F, Willheim M, et al. The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells. Blood. 1997;90:4438–49.
- Bradding P, Brightling C. Mast cell infiltration of airway smooth muscle in asthma. Respir Med. 2007;101:1045. Author reply 1046–7. CrossRef
- El-Shazly A, Berger P, Girodet PO, Ousova O, Fayon M, Vernejoux JM, et al. Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma. J Immunol. 2006;176:1860–8.
- Halayko AJ, Tran T, Ji SY, Yamasaki A, Gosens R. Airway smooth muscle phenotype and function: interactions with current asthma therapies. Current Drug Targets. 2006;7:525–40. CrossRef
- Nilsson G, Blom T, Kusche-Gullberg M, Kjellen L, Butterfield JH, Sundstrom C, et al. Phenotypic characterization of the human mast-cell line HMC-1. Scand J Immunol. 1994;39:489–98. CrossRef
- Brightling CE, Kaur D, Berger P, Morgan AJ, Wardlaw AJ, Bradding P. Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration. J Leukoc Biol. 2005;77:759–66. CrossRef
- Brightling CE, Ammit AJ, Kaur D, Black JL, Wardlaw AJ, Hughes JM, et al. The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med. 2005;171:1103–8. CrossRef
- Kaur D, Saunders R, Berger P, Siddiqui S, Woodman L, Wardlaw A, et al. Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma. Am J Respir Crit Care Med. 2006;174:1179–88. CrossRef
- Marone G, Triggiani M, Genovese A, Paulis AD. Role of human mast cells and basophils in bronchial asthma. Adv Immunol. 2005;88:97–160. CrossRef
- IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation
Volume 59, Issue 3 , pp 207-218
- Cover Date
- Print ISSN
- Online ISSN
- SP Birkhäuser Verlag Basel
- Additional Links
- ST2 signaling
- IgE receptor
- Adenosine receptors
- RTK signaling
- Industry Sectors
- Author Affiliations
- 1. Inflammation Research, Wyeth, 200 Cambridge Park Drive, Cambridge, MA, 02140, USA
- 2. Cell Signaling Technology, Danvers, MA, USA
- 3. Genzyme, Farmingham, MA, USA