Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1
Hannu Kankaanranta, Pinja Ilmarinen, Xianzhi Zhang, Ian M Adcock, Aleksi Lahti, Peter J Barnes, Mark A Giembycz, Mark A Lindsay, Eeva Moilanen, Hannu Kankaanranta, Pinja Ilmarinen, Xianzhi Zhang, Ian M Adcock, Aleksi Lahti, Peter J Barnes, Mark A Giembycz, Mark A Lindsay, Eeva Moilanen
Abstract
Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
- Wenzel SE (2009) Eosinophils in asthma – closing the loop or opening the door? N Engl J Med 360: 1026–1028.
- Watt AP, Schock BC, Ennis M (2005) Neutrophils and eosinophils: clinical implications of their appearance, presence and disappearance in asthma and COPD. Curr Drug Targets Inflamm Allergy 4: 415–23.
- Kankaanranta H, Moilanen E, Zhang X (2005) Pharmacological regulation of human eosinophil apoptosis. Curr Drug Targets Inflamm Allergy 4: 433–45.
- Walsh GM (2013) Eosinophil apoptosis and clearance in asthma. J Cell Death 6: 17–25.
- Simon H-U (2009) Cell death in allergic diseases. Apoptosis 14: 439–446.
- Duffin R, Leitch AE, Fox S, Haslett C, Rossi AG (2010) Targeting granulocyte apoptosis: mechanisms, models, and therapies. Immunol Rev 236: 28–40.
- Keystone EC, Ware CF (2010) Tumor necrosis factor and anti-tumor necrosis factor therapies. J Rheumatol 37 Suppl 8527–39.
- Matera MG, Calzetta L, Cazzola M (2010) TNF-α inhibitors in asthma and COPD: we must not throw the baby out with the bath water. Pulm Pharm Ther 23: 121–128.
- Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, et al. (2009) A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma. Am J Respir Crit Care Med 179: 549–558.
- Rennard IS, Fogarty C, Kelsen S, Long W, Ramsdell J, et al. (2007) The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175: 926–934.
- Li H, Lin X (2008) Positive and negative signalling components involved in TNFα-induced NF-κB activation. Cytokine 41: 1–8.
- Tchikov V, Betsch U, Fritsch J, Edelmann B, Schütze S (2011) Subcellular compartmentalization of TNF receptor-1 and CD95 signaling pathways. Eur J Cell Biol 90: 467–475.
- Levi-Schaffer F, Temkin V, Malamud V, Feld S, Zilberman Y (1998) Mast cells enhance eosinophil survival in vitro: role of TNF-α and granulocyte-macrophage colony-stimulating factor. J Immunol 160: 5554–5562.
- Tsukahara K, Nakao A, Hiraguri M, Miike S, Mamura M, et al. (1999) Tumor necrosis factor-α mediates antiapoptotic signals partially via p38 MAP kinase activation in human eosinophils. Int Arch Allergy Immunol 120 (suppl 1)54–59.
- Fujihara S, Ward C, Dransfield I, Hay RT, Uings IJ, et al. (2002) Inhibition of nuclear factor-κB activation un-masks the ability of TNF-α to induce human eosinophil apoptosis. Eur J Immunol 32: 457–466.
- Ward C, Chilvers ER, Lawson MF, Pryde JG, Fujihara S, et al. (1999) NF-κB activation is a critical regulator of human granulocyte apoptosis in vitro. J Biol Chem 274: 4309–4318.
- Temkin V, Levi-Schaffer F (2001) Mechanism of tumour necrosis factor alpha mediated eosinophil survival. Cytokine 15: 20–26.
- Kankaanranta H, Lindsay MA, Giembycz MA, Zhang X, Moilanen E, et al. (2000) Delayed eosinophil apoptosis in asthma. J Allergy Clin Immunol 106: 77–83.
- Wedi B, Raap U, Lewrick H, Kapp A (1997) Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis. J Allergy Clin Immunol 100: 536–543.
- Brightling C, Berry M, Amrani Y (2008) Targeting TNF-α: a novel therapeutic approach for asthma. J Allergy Clin Immunol 121: 5–10.
- Ilmarinen P, Hasala H, Sareila O, Moilanen E, Kankaanranta H (2009) Bacterial DNA delays human eosinophil apoptosis. Pulm Pharmacol Ther 22: 167–176.
- Kankaanranta H, De Souza PM, Barnes PJ, Salmon M, Giembycz MA, et al. (1999) SB 203580, an inhibitor of p38 mitogen-activated protein kinase, enhances constitutive apoptosis of cytokine-deprived human eosinophils. J Pharmacol Exp Ther 290: 621–8.
- Kankaanranta H, Ilmarinen P, Zhang X, Nissinen E, Moilanen E (2006) Antieosinophilic activity of orazipone. Mol Pharmacol 69: 1861–70.
- Lahti A, Jalonen U, Kankaanranta H, Moilanen E (2003) c-jun NH2-terminal kinase inhibitor anthra(1,9-cd)pyrazol-6(2H)-one reduces inducible nitric-oxide synthase expression by destabilizing mRNA in activated macrophages. Mol Pharmacol 64: 308–315.
- Ilmarinen-Salo P, Moilanen E, Kankaanranta H (2010) Nitric oxide induces apoptosis in GM-CSF-treated eosinophils via caspase-6-dependent lamin and DNA fragmentation Pulm Pharmacol Ther. 23: 365–371.
- Kankaanranta H, Parkkonen J, Ilmarinen-Salo P, Giembycz MA, Moilanen E (2011) Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism. Pulm Pharmacol Ther 24: 394–400.
- Ilmarinen P, Kankaanranta H (2014) Eosinophil apoptosis as a therapeutic target in allergic asthma. Basic Clin Pharmacol Toxicol 114: 109–117.
- Zhang X, Moilanen E, Adcock IM, Lindsay MA, Kankaanranta H (2002) Divergent effect of mometasone on human eosinophil and neutrophil apoptosis. Life Sci 71: 1523–1534.
- Giembycz MA, Lindsay MA (1999) Pharmacology of the eosinophil. Pharmacol Rev 51: 213–340.
- Druilhe A, Cai Z, Haile S, Chouaib S, Pretolani M (1996) Fas-mediated apoptosis in cultured human eosinophils. Blood 87: 2822–2830.
- Hebestreit H, Yousefi S, Balatti I, Weber M, Crameri R, et al. (1996) Expression and function of the Fas receptor on human blood and tissue eosinophils. Eur J Immunol 26: 1775–1780.
- Matsumoto K, Schleimer RP, Saito H, Iikura Y, Bochner BS (1995) Induction of apoptosis in human eosinophils by anti-Fas antibody treatment in vitro. Blood 86: 1437–1443.
- Adcock IM (2000) Role of transcription factors in mediating cytokine-induced inflammation. Eur Respir J 10: 289–293.
- Pahl HL, Krauβ, Schulze-Osthoff K, Decker T, Traenckner EB-M, et al. (1996) The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-κB. J Exp Med 183: 1829–1840.
- Schreck R, Meier B, Männel DN, Dröge W, Baeuerle PA (1992) Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med 175: 1181–1194.
- Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, et al. (2003) BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice. J Biol Chem 278: 1450–1456.
- Fanjul A, Dawson MI, Hobbs PD, Jong L, Cameron JF, et al. (1994) A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature 372: 107–111.
- Sung HJ, Choi SM, Yoon Y, An KS (1999) Tanshinone IIA, an ingredient of Salvia mitiorrhiza BUNGE, induces apoptosis in human leukaemia cell lines through the activation of caspase-3. Exp Mol Med 31: 174–178.
- Gaur U, Aggarwal BB (2003) Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol 66: 1403–1408.
- Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differentation 10: 45–65.
- Eferl R, Wagner EF (2003) AP-1: A double-edged sword in tumorigenesis. Nature Rev Cancer 3: 859–868.
- Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nature Cell Biol 4: E131–E136.
- De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, et al. (2001) Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling. Nature 414: 308–313.
- Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, et al. (2001) Inhibition of JNK activation through NF-κB target genes. Nature 414: 313–317.
- Liu H, Lo CR, Czaja MJ (2002) NF-κB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-jun. Hepatology 35: 772–778.
- Kriehuber E, Bauer W, Charbonnier A-S, Winter D, Amatschek S, et al. (2005) Balance between NF-κB and JNK/AP-1 activity controls dendritic cell life and death. Blood 106: 175–183.
- Park YM, Bochner BS (2010) Eosinophil survival and apoptosis in health and disease. Allergy Asthma Immunol Res 2: 87–101.
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