Abstract
The pleiotropic cytokine TNF-α has been implicated in airway inflammation and airway hyperresponsiveness (AHR), hallmark features of asthma. Polymorphisms in the TNF gene cluster are associated with increased TNF-α production and risk of asthma. Our laboratory has demonstrated that in human airway smooth muscle (HASM) cells, TNF-α augments the expression of CD38, a type II transmembrane glycoprotein which synthesizes the calcium-mobilizing molecule cyclic ADP-ribose. Mice challenged intranasally with TNF-α develop AHR to inhaled methacholine. However, mice that are deficient in CD38 fail to develop AHR, indicating that CD38 expressed in the airways is required for cytokine-induced AHR. In HASM cells, TNF-α-induced CD38 expression is decreased in the presence of inhibitors of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs). The decreased CD38 expression by p38 and JNK MAPK inhibitors is associated with decreased activation of NF-κB, whereas the decrease by the ERK MAPK inhibitor is due to decreased stability of CD38 transcripts. TNF-α induced a twofold activation of a 3 kb cd38 promoter following its transfection in HASM cells. However, there was no activation of the promoter lacking the NF-κB site. These results demonstrate that TNF-α regulation of CD38 expression in HASM cells is mediated transcriptionally through p38 and JNK MAPKs and NF-κB and post-transcriptionally through the ERK MAPK. These findings support a role for CD38/cADPR signaling in TNF-α-induced AHR.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adcock IM, Tsaprouni L, Bhavsar P et al (2007) Epigenetic regulation of airway inflammation. Curr Opin Immunol 19(6):694–700
Albuquerque RV, Hayden CM, Palmer LJ et al (1998) Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma. Clin Exp Allergy 28: 578–584
Amrani Y, Ammit AJ, Panettieri RA Jr (2001) Tumor necrosis factor receptor (TNFR) 1, but not TNFR2, mediates tumor necrosis factor-alpha-induced interleukin-6 and RANTES in human airway smooth muscle cells: role of p38 and p42/44 mitogen-activated protein kinases. Mol Pharmacol 60:646–655
Antoniu SA (2009) Golimumab for severe asthma. Expert Opin Investig Drugs 18:1421–1423
Barata H, Thompson M, Zielinska W et al (2004) The role of cyclic-ADP-ribose-signaling pathway in oxytocin-induced Ca2+ transients in human myometrium cells. Endocrinology 145:881–889
Berry MA, Hargadon B, Shelley M et al (2006) Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 354:697–708
Bilolikar H, Nam AR, Rosenthal M et al (2005) Tumour necrosis factor gene polymorphisms and childhood wheezing. Eur Respir J 26:637–646
Bousquet J, Jacot W, Yssel H et al (2004) Epigenetic inheritance of fetal genes in allergic asthma. Allergy 59(2):138–147
Broide DH, Lotz M, Cuomo AJ et al (1992) Cytokines in symptomatic asthma airways. J Allergy Clin Immunol 89:958–967
Chue SC, Seow CJ, Duan W et al (2004) Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro. Int Immunopharmacol 4:1089–1098
Deshpande DA, Dogan S, Walseth TF et al (2004) Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway. Am J Respir Cell Mol Biol 31:36–42
Deshpande DA, Walseth TF, Panettieri RA et al (2003) CD38/cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyper-responsiveness. FASEB J 17:452–454
Deshpande DA, White TA, Dogan S et al (2005a) CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 288, L773–L788
Deshpande DA, White TA, Guedes AG et al (2005b) Altered airway responsiveness in CD38-deficient mice. Am J Respir Cell Mol Biol 32:149–156
Desmet C, Gosset P, Henry E et al (2005) Treatment of experimental asthma by decoy-mediated local inhibition of activator protein-1. Am J Respir Crit Care Med 172:671–678
Desmet C, Gosset P, Pajak B et al (2004) Selective blockade of NF-kappa B activity in airway immune cells inhibits the effector phase of experimental asthma. J Immunol 173:5766–5775
Dipp M, Evans AM (2001) Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction in the rat lung in situ. Circ Res 89:77–83
Duan W, Chan JH, McKay K et al (2005). Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care Med 171:571–578
Durig J, Naschar M, Schmucker U et al (2002) CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia 16:30–35
Edwards MR, Bartlett NW, Clarke D et al (2009) Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol Ther 121:1–13
Erin EM, Leaker BR, Nicholson GC et al (2006) The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 174:753–762
Erzurum SC (2006) Inhibition of tumor necrosis factor alpha for refractory asthma. N Engl J Med 354:754–758
Ferrero E, Saccucci F, Malavasi F (1999) The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene. Immunogenetics 49:597–604
Frishman JI, Edwards CK, Sonnenberg MG et al (2000) Tumor necrosis factor (TNF)-alpha-induced interleukin-8 in human blood cultures discriminates neutralization by the p55 and p75 TNF soluble receptors. J Infect Dis 182:1722–1730
Graeff R, Liu Q, Kriksunov IA et al (2006) Acidic residues at the active sites of CD38 and ADP-ribosyl cyclase determine nicotinic acid adenine dinucleotide phosphate (NAADP) synthesis and hydrolysis activities. J Biol Chem 281:28951–28957
Graeff R, Liu Q, Kriksunov IA et al (2009) Mechanism of cyclizing NAD to cyclic ADP-ribose by ADP-ribosyl cyclase and CD38. J Biol Chem 284 (40):27629–27636
Guedes AG, Jude JA, Paulin J (2008) Role of CD38 in TNF-alpha-induced airway hyperresponsiveness. Am J Physiol Lung Cell Mol Physiol 294, L290–L299
Guedes AG, Paulin J, Rivero-Nava L (2006) CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge. Am J Physiol Lung Cell Mol Physiol 291:L1286–L1293
Hart LA, Krishnan VL, Adcock IM et al (1998) Activation and localization of transcription factor, nuclear factor-kappaB, in asthma. Am J Respir Crit Care Med 158:1585–1592
Higashida H, Hashii M, Yokoyama S et al (2001) Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling. J Neurochem 76:321–331
Holgate ST, Yang Y, Haitchi HM et al (2006) The genetics of asthma: ADAM33 as an example of a susceptibility gene. Proc Am Thoracic Soc 3(5):440–443
Howard M, Grimaldi JC, Bazan JF et al (1993) Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science 262:1056–1059
Howarth PH, Babu KS, Arshad HS et al (2005) Tumour necrosis factor (TNF)-alpha as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 60:1012–1018
Ikehata F, Satoh J, Nata K et al (1998) Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients. J Clin Invest 102:395–401
Issa R, Xie S, Lee KY et al (2006) GRO-alpha regulation in airway smooth muscle by IL-1beta and TNF-alpha: role of NF-kappaB and MAP kinases. Am J Physiol Lung Cell Mol Physiol 291:L66–L74
Kang BN, Deshpande DA, Tirumurugaan KG et al (2005) Adenoviral mediated anti-sense CD38 attenuates TNF-alpha-induced changes in calcium homeostasis of human airway smooth muscle cells. Can J Physiol Pharmacol 83:799–804
Kang BN, Jude JA, Panettieri RA Jr et al (2008) Glucocorticoid regulation of CD38 expression in human airway smooth muscle cells: role of dual specificity phosphatase 1. Am J Physiol Lung Cell Mol Physiol 295, L186–L193
Kang BN, Tirumurugaan KG, Deshpande DA et al (2006) Transcriptional regulation of CD38 expression by tumor necrosis factor-alpha in human airway smooth muscle cells: role of NF-kappaB and sensitivity to glucocorticoids. FASEB J 20, E170–E179
Kishimoto H, Hoshino S, Ohori M et al (1998) Molecular mechanism of human CD38 gene expression by retinoic acid. Identification of retinoic acid response element in the first intron. J Biol Chem 273:15429–15434
Lee HC (2000) Enzymatic functions and structures of CD38 and homologs. Chem Immunol 75:39–59
Lee HC, Aarhus R (1991) ADP-ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite. Cell Regul 2:203–209
Li YF, Gauderman WJ, Avol E et al (2006) Associations of tumor necrosis factor G-308A with childhood asthma and wheezing. Am J Respir Crit Care Med 173:970–976
Liu Q, Graeff R, Kriksunov IA et al (2009) Structural basis for enzymatic evolution from a dedicated ADP-ribosyl cyclase to a multi- functional NAD hydrolase. J Biol Chem 284(40):27637–27645
Liu W, Liang Q, Balzar S et al (2008) Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways. J Allergy Clin Immunol 121:893–902
Malavasi F, Deaglio S, Funaro A et al (2008) Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev 88:841–886
Matsuoka T, Kajimoto Y, Watada H et al (1995) Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. Biochem Biophys Res Commun 214:239–246
Nata K, Takamura T, Karasawa T et al (1997) Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing. Gene 186:285–292
Newton R, Hart LA, Stevens DA et al (1998) Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor-kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells. Eur J Biochem 254:81–89
Newton R, Holden NS, Catley MC et al (2007) Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IkappaB kinase inhibitors. J Pharmacol Exp Ther 321:734–742
Noguchi N, Takasawa S, Nata K et al (1997) Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. J Biol Chem 272:3133–3136
Ortolan E, Vacca P, Capobianco A et al (2002) CD157, the Janus of CD38 but with a unique personality. Cell Biochem Funct 20:309–322
Perera F, Tang WY, Herbstman J et al (2009) Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4(8) doi: 10.1371/annotation/6a678269-9623-4a13-8b19-4e9431ff3cb6
Prakash YS, Kannan MS, Walseth TF et al (1998) Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle Am J Physiol 274:C1653–C1660
Schottelius AJ, Moldawer LL, Dinarello CA et al (2004) Biology of tumor necrosis factor-alpha- implications for psoriasis. Exp Dermatol 13:193–222
Sieck GC, White TA, Thompson MA et al (2008) Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 294:L378–L385
Sun L, Iqbal J, Zaidi S et al (2006) Structure and functional regulation of the CD38 promoter. Biochem Biophys Res Commun 341:804–809
Tang WX, Chen YF, Zou AP et al (2002) Role of FKBP12.6 in cADPR-induced activation of reconstituted ryanodine receptors from arterial smooth muscle. Am J Physiol Heart Circ Physiol 282:H1304–H310
Thomas PS (2001) Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma. Immunol Cell Biol 79:132–140
Thomas PS, Yates DH, Barnes PJ (1995) Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med 152:76–80
Tirumurugaan KG, Jude JA, Kang BN et al (2007) TNF-alpha induced CD38 expression in human airway smooth muscle cells: role of MAP kinases and transcription factors NF-kappaB and AP-1. Am J Physiol Lung Cell Mol Physiol 292, L1385–L1395
Tirumurugaan KG, Kang BN, Panettieri RA et al (2008) Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha and dexamethasone. Respir Res 9:26, doi: 10.1186/1465-9921-9-26.
Wang CC, Lin WN, Lee CW et al (2005) Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-kappaB in IL-1beta-induced VCAM-1 expression in human tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 288:L227–L237
Wenzel SE, Barnes PJ, Bleecker ER et al (2009) A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 179:549–558
White TA, Kannan MS, Walseth TF (2003) Intracellular calcium signaling through the cADPR pathway is agonist specific in porcine airway smooth muscle. FASEB J 17:482–484
Ying S, Robinson DS, Varney V et al (1991) TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy 21:745–750
Zhou L, Tan A, Iasvovskaia S et al (2003) Ras and mitogen-activated protein kinase kinase kinase-1 coregulate activator protein-1- and nuclear factor-kappaB-mediated gene expression in airway epithelial cells. Am J Respir Cell Mol Biol 28:762–769
Acknowledgments
Work cited in this chapter is supported by grants from the National Institutes of Health (HL057498 to MSK) and (DA-11806 to TFW). We thank Drs. Tirumurugaan, Kang, and Guedes for their contribution.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this paper
Cite this paper
Jude, J.A., Panettieri, R.A., Walseth, T.F., Kannan, M.S. (2011). TNF-α Regulation of CD38 Expression in Human Airway Smooth Muscle: Role of MAP Kinases and NF-κB. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_46
Download citation
DOI: https://doi.org/10.1007/978-1-4419-6612-4_46
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-6611-7
Online ISBN: 978-1-4419-6612-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)