All Title Author
Keywords Abstract

PLOS ONE  2011 

NF-κB Inducing Kinase, NIK Mediates Cigarette Smoke/TNFα-Induced Histone Acetylation and Inflammation through Differential Activation of IKKs

DOI: 10.1371/journal.pone.0023488

Full-Text   Cite this paper   Add to My Lib

Abstract:

Background Nuclear factor (NF)-κB inducing kinase (NIK) is a central player in the non-canonical NF κB pathway, which phosphorylates IκB kinase α (IKKα) resulting in enhancement of target gene expression. We have recently shown that IKKα responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-κB activation. However, the primary signaling mechanism linking CS-mediated oxidative stress and TNFα with histone acetylation and pro-inflammatory gene transcription is not well understood. We hypothesized that CS and TNFα increase NIK levels causing phosphorylation of IKKα, which leads to histone acetylation. Methodology To test this hypothesis, we investigated whether NIK mediates effects of CS and TNFα on histone acetylation in human lung epithelial cells in vitro and in lungs of mouse exposed to CS in vivo. CS increased the phosphorylation levels of IKKα/NIK in lung epithelial cells and mouse lungs. NIK is accumulated in the nuclear compartment, and is recruited to the promoters of pro-inflammatory genes, to induce posttranslational acetylation of histones in response to CS and TNFα. Cells in which NIK is knocked down using siRNA showed partial attenuation of CSE- and TNFα-induced acetylation of histone H3 on pro-inflammatory gene promoters. Additional study to determine the role of IKKβ/NF-κB pathway in CS-induced histone acetylation suggests that the canonical pathway does not play a role in histone acetylation particularly in response to CS in mouse lungs. Conclusions Overall, our findings provide a novel role for NIK in CS- and TNFα-induced histone acetylation, especially on histone H3K9.

References

[1]  Church DF, Pryor WA (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 64: 111–126.
[2]  Moghaddam SJ, Li H, Cho SN, Dishop MK, Wistuba , et al. (2009) Promotion of lung carcinogenesis by chronic obstructive pulmonary disease-like airway inflammation in a K-ras-induced mouse model. Am J Respir Cell Mol Biol 40: 443–453.
[3]  Yao H, Rahman I (2009) Current concepts on the role of inflammation in COPD and lung cancer. Curr Opin Pharmacol 9: 375–383.
[4]  Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, et al. (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350: 2645–2653.
[5]  Hogg JC (2004) Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364: 709–721.
[6]  Chung KF, Adcock IM (2008) Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 31: 1334–1356.
[7]  Rajendrasozhan S, Yang SR, Edirisinghe I, Yao H, Adenuga D, et al. (2008) Deacetylases and NF-kappaB in redox regulation of cigarette smoke-induced lung inflammation: epigenetics in pathogenesis of COPD. Antioxid Redox Signal 10: 799–811.
[8]  Yao H, Rahman I (2011) Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol Appl Pharmacol 254: 72–85.
[9]  Yang SR, Valvo S, Yao H, Kode A, Rajendrasozhan S, et al. (2008) IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung. Am J Respir Cell Mol Biol 38: 689–698.
[10]  Yao H, Hwang JW, Moscat J, Diaz-Meco MT, Leitges M, et al. (2010) Protein kinase C zeta mediates cigarette smoke/aldehyde- and lipopolysaccharide-induced lung inflammation and histone modifications. J Biol Chem 285: 5405–5416.
[11]  Caito S, Rajendrasozhan S, Cook S, Chung S, Yao H, et al. (2010) SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stress. FASEB J 24: 3145–3159.
[12]  Kode A, Yang SR, Rahman I (2006) Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells. Respir Res 7: 132.
[13]  Cao D, Bromberg PA, Samet JM (2007) COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1. Am J Respir Cell Mol Biol 37: 232–239.
[14]  Gilmour PS, Rahman I, Donaldson K, MacNee W (2003) Histone acetylation regulates epithelial IL-8 release mediated by oxidative stress from environmental particles. Am J Physiol Lung Cell Mol Physiol 284: L533–540.
[15]  Rahman I, Antonicelli F, MacNee W (1999) Molecular mechanism of the regulation of glutathione synthesis by tumor necrosis factor-alpha and dexamethasone in human alveolar epithelial cells. J Biol Chem 274: 5088–5096.
[16]  Moodie FM, Marwick JA, Anderson CS, Szulakowski P, Biswas SK, et al. (2004) Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-kappaB activation and proinflammatory cytokine release in alveolar epithelial cells. FASEB J 18: 1897–1899.
[17]  Rahman I, MacNee W (1998) Role of transcription factors in inflammatory lung diseases. Thorax 53: 601–612.
[18]  Kim JY, Morgan M, Kim DG, Lee JY, Bai L, et al. (2011) TNFalpha induced noncanonical NF-kappaB activation is attenuated by RIP1 through stabilization of TRAF2. J Cell Sci 124: 647–656.
[19]  Ito K, Ito M, Elliott WM, Cosio B, Caramori G, et al. (2005) Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 352: 1967–1976.
[20]  Szulakowski P, Crowther AJ, Jimenez LA, Donaldson K, Mayer R, et al. (2006) The effect of smoking on the transcriptional regulation of lung inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 174: 41–50.
[21]  Marwick JA, Kirkham PA, Stevenson CS, Danahay H, Giddings J, et al. (2004) Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol 31: 633–642.
[22]  Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389: 349–352.
[23]  Rahman I, Marwick J, Kirkham P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol 68: 1255–1267.
[24]  Chung S, Sundar IK, Yao H, Ho YS, Rahman I (2010) Glutaredoxin 1 regulates cigarette smoke-mediated lung inflammation through differential modulation of I{kappa}B kinases in mice: impact on histone acetylation. Am J Physiol Lung Cell Mol Physiol 299: L192–203.
[25]  O'Mahony A, Lin X, Geleziunas R, Greene WC (2000) Activation of the heterodimeric IkappaB kinase alpha (IKKalpha)-IKKbeta complex is directional: IKKalpha regulates IKKbeta under both basal and stimulated conditions. Mol Cell Biol 20: 1170–1178.
[26]  Zarnegar B, Yamazaki S, He JQ, Cheng G (2008) Control of canonical NF-kappaB activation through the NIK-IKK complex pathway. Proc Natl Acad Sci (USA) 105: 3503–3508.
[27]  Adli M, Merkhofer E, Cogswell P, Baldwin AS (2010) IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PLoS One 5: e9428.
[28]  Rajendrasozhan S, Hwang JW, Yao H, Kishore N, Rahman I (2010) Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke. Pulm Pharmacol Ther 23: 172–181.
[29]  Shuto T, Xu H, Wang B, Han J, Kai H, et al. (2001) Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha/beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc Natl Acad Sci (USA) 98: 8774–8779.
[30]  Yang SR, Yao H, Rajendrasozhan S, Chung S, Edirisinghe I, et al. (2009) RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke. Am J Respir Cell Mol Biol 40: 147–158.
[31]  Cheng DS, Han W, Chen SM, Sherrill TP, Chont M, et al. (2007) Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway. J Immunol 178: 6504–6513.
[32]  Chen SM, Cheng DS, Williams BJ, Sherrill TP, Han W, et al. (2008) The nuclear factor kappa-B pathway in airway epithelium regulates neutrophil recruitment and host defence following Pseudomonas aeruginosa infection. Clin Exp Immunol 153: 420–428.
[33]  Yao H, Edirisinghe I, Rajendrasozhan S, Yang SR, Caito S, et al. (2008) Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice. Am J Physiol Lung Cell Mol Physiol 294: L1174–1186.
[34]  Rodkey FL, Hill TA, Pitts LL, Robertson RF (1979) Spectrophotometric measurement of carboxyhemoglobin and methemoglobin in blood. Clin Chem 25: 1388–1393.
[35]  Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I (2008) SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177: 861–870.
[36]  Birbach A, Gold P, Binder BR, Hofer E, de Martin R, et al. (2002) Signaling molecules of the NF-kappa B pathway shuttle constitutively between cytoplasm and nucleus. J Biol Chem 277: 10842–10851.
[37]  Park GY, Wang X, Hu N, Pedchenko TV, Blackwell TS, et al. (2006) NIK is involved in nucleosomal regulation by enhancing histone H3 phosphorylation by IKKalpha. J Biol Chem 281: 18684–18690.
[38]  Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB (2003) Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature 423: 655–659.
[39]  Lam LT, Davis RE, Ngo VN, Lenz G, Wright G, et al. (2008) Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta inhibition identified by an RNA interference sensitization screen. Proc Natl Acad Sci (USA) 105: 20798–20803.
[40]  Sun SC (2010) Controlling the fate of NIK: a central stage in noncanonical NF-kappaB signaling. Sci Signal 3: pe18.
[41]  Li Q, Engelhardt JF (2006) Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated activation of NFkappaB-inducing kinase. J Biol Chem 281: 1495–1505.
[42]  Song YS, Kim MS, Kim HA, Jung BI, Yang J, et al. (2010) Oxidative stress increases phosphorylation of IkappaB kinase-alpha by enhancing NF-kappaB-inducing kinase after transient focal cerebral ischemia. J Cereb Blood Flow Metab 30: 1265–1274.
[43]  Tuder RM (2006) Aging and cigarette smoke: fueling the fire. Am J Respir Crit Care Med 174: 490–491.
[44]  Azim AC, Wang X, Park GY, Sadikot RT, Cao H, et al. (2007) NF-kappaB-inducing kinase regulates cyclooxygenase 2 gene expression in macrophages by phosphorylation of PU.1. J Immunol 179: 7868–7875.
[45]  Razani B, Zarnegar B, Ytterberg AJ, Shiba T, Dempsey PW, et al. (2010) Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. Sci Signal 3: ra41.
[46]  Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (1997) IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 278: 866–869.
[47]  Ling L, Cao Z, Goeddel DV (1998) NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc Natl Acad Sci (US A) 95: 3792–3797.
[48]  Thu YM, Richmond A (2010) NF-kappaB inducing kinase: a key regulator in the immune system and in cancer. Cytokine Growth Factor Rev 21: 213–226.
[49]  Sanjo H, Zajonc DM, Braden R, Norris PS, Ware CF (2010) Allosteric regulation of the ubiquitin:NIK and ubiquitin:TRAF3 E3 ligases by the lymphotoxin-beta receptor. J Biol Chem 285: 17148–17155.
[50]  Sun SC (2011) Non-canonical NF-kappaB signaling pathway. Cell Res 21: 71–85.
[51]  Birbach A, Bailey ST, Ghosh S, Schmid JA (2004) Cytosolic, nuclear and nucleolar localization signals determine subcellular distribution and activity of the NF-kappaB inducing kinase NIK. J Cell Sci 117: 3615–3624.
[52]  Jiang X, Takahashi N, Ando K, Otsuka T, Tetsuka T, et al. (2003) NF-kappa B p65 transactivation domain is involved in the NF-kappa B-inducing kinase pathway. Biochem Biophys Res Commun 301: 583–590.
[53]  Adcock IM, Tsaprouni L, Bhavsar P, Ito K (2007) Epigenetic regulation of airway inflammation. Curr Opin Immunol 19: 694–700.
[54]  Adcock IM, Caramori G, Barnes PJ (2011) Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration 81: 265–284.
[55]  Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, et al. (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40: 897–903.
[56]  Cosio BG, Mann B, Ito K, Jazrawi E, Barnes PJ, et al. (2004) Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med 170: 141–147.
[57]  Barnes PJ, Adcock IM (2009) Glucocorticoid resistance in inflammatory diseases. Lancet 373: 1905–1917.
[58]  Millington GW (2008) Epigenetics and dermatological disease. Pharmacogenomics 9: 1835–1850.
[59]  Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, et al. (2008) In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest 118: 3462–3469.
[60]  Liu F, Killian JK, Yang M, Walker RL, Hong JA, et al. (2010) Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 29: 3650–3664.
[61]  Ghosh S, Hayden MS (2008) New regulators of NF-kappaB in inflammation. Nat Rev Immunol 8: 837–848.
[62]  Hacker H, Karin M (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006. re13 p.
[63]  Huang WC, Ju TK, Hung MC, Chen CC (2007) Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB. Mol Cell 26: 75–87.
[64]  Hirata Y, Maeda S, Ohmae T, Shibata W, Yanai A, et al. (2006) Helicobacter pylori induces IkappaB kinase alpha nuclear translocation and chemokine production in gastric epithelial cells. Infect Immun 74: 1452–1461.
[65]  Anest V, Cogswell PC, Baldwin AS Jr (2004) IkappaB kinase alpha and p65/RelA contribute to optimal epidermal growth factor-induced c-fos gene expression independent of IkappaBalpha degradation. J Biol Chem 279: 31183–31189.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal