Pershagen G, Guerra S, Garcia-Aymerich J, Greco D, Reinius L, McEachan RRC, Azad R,
Hovland V, Mowinckel P, Alenius H, Fyhrquist N, Lemonnier N, Pellet J, Auffray C, van
der Vlies P, van Diemen CC, Li Y, Wijmenga C, Netea MG, Moffatt MF, Cookson WOCM,
Anto JM, Bousquet J, Laatikainen T, Laprise C, Carlsen KH, Gori D, Porta D, Iñiguez C,
Bilbao JR, Kogevinas M, Wright J, Brunekreef B, Kere J, Nawijn MC, Annesi-Maesano I,
Sunyer J, Melén E, Koppelman GH (2018) DNA methylation in childhood asthma: an
epigenome-wide meta-analysis. Lancet Respir Med 6:379–388. https://doi.org/10.1016/
S2213-2600(18)30052-3
103. Cheng RYS, Shang Y, Limjunyawong N, Dao T, Das S, Rabold R, Sham JSK, Mitzner W,
Tang W-Y (2014) Alterations of the lung methylome in allergic airway hyper-responsiveness.
Environ Mol Mutagen 55:244–255. https://doi.org/10.1002/em.21851
104. Shang Y, Das S, Rabold R, Sham JSK, Mitzner W, Tang WY (2013) Epigenetic alterations by
DNA methylation in house dust mite-induced airway hyperresponsiveness. Am J Respir Cell
Mol Biol 49:279–287. https://doi.org/10.1165/rcmb.2012-0403OC
105. Wu C-J, Yang C-Y, Chen Y-H, Chen C-M, Chen L-C, Kuo M-L (2013) The DNA methylation
inhibitor 5-azacytidine increases regulatory T cells and alleviates airway inflammation in
ovalbumin-sensitized mice. Int Arch Allergy Immunol 160:356–364. https://doi.org/10.
1159/000343030
106. Sun Q, Yang X, Zhong B, Jiao F, Li C, Li D, Lan X, Sun J, Lu S (2012) Upregulated protein
arginine methyltransferase 1 by IL-4 increases Eotaxin-1 expression in airway epithelial cells
and participates in antigen-induced pulmonary inflammation in rats. J Immunol
188:3506–3512. https://doi.org/10.4049/jimmunol.1102635
107. Sun Q, Liu L, Wang H, Mandal J, Khan P, Hostettler KE, Stolz D, Tamm M, Molino A,
Lardinois D, Lu S, Roth M (2017) Constitutive high expression of protein arginine
methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced
microRNA-19a expression and leads to enhanced remodeling. J Allergy Clin Immunol
140:510–524.e3. https://doi.org/10.1016/j.jaci.2016.11.013
108. Sun Q, Liu L, Roth M, Tian J, He Q, Zhong B, Bao R, Lan X, Jiang C, Sun J, Yang X, Lu S
(2015) PRMT1 upregulated by epithelial proinflammatory cytokines participates in COX2
expression in fibroblasts and chronic antigen-induced pulmonary inflammation. J Immunol
195:298–306. https://doi.org/10.4049/jimmunol.1402465
109. Liu L, Sun Q, Bao R, Roth M, Zhong B, Lan X, Tian J, He Q, Li D, Sun J, Yang X, Lu S
(2016) Specific regulation of PRMT1 expression by PIAS1 and RKIP in BEAS-2B epithelia
cells and HFL-1 fibroblasts in lung inflammation. Sci Rep 6:1–13. https://doi.org/10.1038/
srep21810
110. Ahmad T, Mabalirajan U, Ghosh B, Agrawal A (2010) Altered asymmetric dimethyl arginine
metabolism in allergically inflamed mouse lungs. Am J Respir Cell Mol Biol 42:3–8. https://
doi.org/10.1165/rcmb.2009-0137RC
111. Klein E, Weigel J, Buford MC, Holian A, Wells SM (2010) Asymmetric dimethylarginine
potentiates lung inflammation in a mouse model of allergic asthma. Am J Phys 299:L816–
L825. https://doi.org/10.1152/ajplung.00188.2010
112. He X, Li T, Kang N, Zeng H, Ren S, Zong D, Li J, Cai S, Chen P, Chen Y (2017)
The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine
emphysema model. Int J COPD 12:3245–3254. https://doi.org/10.2147/COPD.S144881
113. McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ (2016)
Recent progress in histone demethylase inhibitors. J Med Chem 59:1308–1329. https://doi.
org/10.1021/acs.jmedchem.5b01758
114. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M,
Gerlach LO, Birk P, Helin K (2014) Inhibition of demethylases by GSK-J1/J4. Nature 514:
E1–E2. https://doi.org/10.1038/nature13688
115. Clifford RL, John AE, Brightling CE, Knox AJ (2012) Abnormal histone methylation is
responsible for increased vascular endothelial growth factor 165a secretion from airway
smooth muscle cells in asthma. J Immunol 189:819–831. https://doi.org/10.4049/jimmunol.
1103641
452
M. R. H. Zwinderman et al.
Hovland V, Mowinckel P, Alenius H, Fyhrquist N, Lemonnier N, Pellet J, Auffray C, van
der Vlies P, van Diemen CC, Li Y, Wijmenga C, Netea MG, Moffatt MF, Cookson WOCM,
Anto JM, Bousquet J, Laatikainen T, Laprise C, Carlsen KH, Gori D, Porta D, Iñiguez C,
Bilbao JR, Kogevinas M, Wright J, Brunekreef B, Kere J, Nawijn MC, Annesi-Maesano I,
Sunyer J, Melén E, Koppelman GH (2018) DNA methylation in childhood asthma: an
epigenome-wide meta-analysis. Lancet Respir Med 6:379–388. https://doi.org/10.1016/
S2213-2600(18)30052-3
103. Cheng RYS, Shang Y, Limjunyawong N, Dao T, Das S, Rabold R, Sham JSK, Mitzner W,
Tang W-Y (2014) Alterations of the lung methylome in allergic airway hyper-responsiveness.
Environ Mol Mutagen 55:244–255. https://doi.org/10.1002/em.21851
104. Shang Y, Das S, Rabold R, Sham JSK, Mitzner W, Tang WY (2013) Epigenetic alterations by
DNA methylation in house dust mite-induced airway hyperresponsiveness. Am J Respir Cell
Mol Biol 49:279–287. https://doi.org/10.1165/rcmb.2012-0403OC
105. Wu C-J, Yang C-Y, Chen Y-H, Chen C-M, Chen L-C, Kuo M-L (2013) The DNA methylation
inhibitor 5-azacytidine increases regulatory T cells and alleviates airway inflammation in
ovalbumin-sensitized mice. Int Arch Allergy Immunol 160:356–364. https://doi.org/10.
1159/000343030
106. Sun Q, Yang X, Zhong B, Jiao F, Li C, Li D, Lan X, Sun J, Lu S (2012) Upregulated protein
arginine methyltransferase 1 by IL-4 increases Eotaxin-1 expression in airway epithelial cells
and participates in antigen-induced pulmonary inflammation in rats. J Immunol
188:3506–3512. https://doi.org/10.4049/jimmunol.1102635
107. Sun Q, Liu L, Wang H, Mandal J, Khan P, Hostettler KE, Stolz D, Tamm M, Molino A,
Lardinois D, Lu S, Roth M (2017) Constitutive high expression of protein arginine
methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced
microRNA-19a expression and leads to enhanced remodeling. J Allergy Clin Immunol
140:510–524.e3. https://doi.org/10.1016/j.jaci.2016.11.013
108. Sun Q, Liu L, Roth M, Tian J, He Q, Zhong B, Bao R, Lan X, Jiang C, Sun J, Yang X, Lu S
(2015) PRMT1 upregulated by epithelial proinflammatory cytokines participates in COX2
expression in fibroblasts and chronic antigen-induced pulmonary inflammation. J Immunol
195:298–306. https://doi.org/10.4049/jimmunol.1402465
109. Liu L, Sun Q, Bao R, Roth M, Zhong B, Lan X, Tian J, He Q, Li D, Sun J, Yang X, Lu S
(2016) Specific regulation of PRMT1 expression by PIAS1 and RKIP in BEAS-2B epithelia
cells and HFL-1 fibroblasts in lung inflammation. Sci Rep 6:1–13. https://doi.org/10.1038/
srep21810
110. Ahmad T, Mabalirajan U, Ghosh B, Agrawal A (2010) Altered asymmetric dimethyl arginine
metabolism in allergically inflamed mouse lungs. Am J Respir Cell Mol Biol 42:3–8. https://
doi.org/10.1165/rcmb.2009-0137RC
111. Klein E, Weigel J, Buford MC, Holian A, Wells SM (2010) Asymmetric dimethylarginine
potentiates lung inflammation in a mouse model of allergic asthma. Am J Phys 299:L816–
L825. https://doi.org/10.1152/ajplung.00188.2010
112. He X, Li T, Kang N, Zeng H, Ren S, Zong D, Li J, Cai S, Chen P, Chen Y (2017)
The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine
emphysema model. Int J COPD 12:3245–3254. https://doi.org/10.2147/COPD.S144881
113. McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ (2016)
Recent progress in histone demethylase inhibitors. J Med Chem 59:1308–1329. https://doi.
org/10.1021/acs.jmedchem.5b01758
114. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M,
Gerlach LO, Birk P, Helin K (2014) Inhibition of demethylases by GSK-J1/J4. Nature 514:
E1–E2. https://doi.org/10.1038/nature13688
115. Clifford RL, John AE, Brightling CE, Knox AJ (2012) Abnormal histone methylation is
responsible for increased vascular endothelial growth factor 165a secretion from airway
smooth muscle cells in asthma. J Immunol 189:819–831. https://doi.org/10.4049/jimmunol.
1103641
452
M. R. H. Zwinderman et al.