#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Hypoxia inhibits TNF-α-induced TSLP expression in keratinocytes


Autoři: Naoyuki Tashiro aff001;  Ryosuke Segawa aff001;  Ryozo Tobita aff001;  Sanki Asakawa aff001;  Natsumi Mizuno aff001;  Masahiro Hiratsuka aff001;  Noriyasu Hirasawa aff001
Působiště autorů: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224705

Souhrn

The expression of thymic stromal lymphopoietin (TSLP), a cytokine which greatly contributes to the induction of type I allergy, is upregulated in chronic inflammation such as atopic dermatitis and psoriasis. As hypoxia in the epidermis is important for maintaining skin homeostasis, we examined the regulation of TSLP expression by hypoxic conditions in normal skin epithelial tissues. TNF-α-induced expression of TSLP in human keratinocyte HaCaT and in mouse keratinocyte PAM212 cell lines were inhibited under hypoxic condition (1% O2), although the mRNA expressions of TNF-α, IL-6, IL-8, MCP-1, and VEGF-A were not inhibited. Hypoxia-mimicking conditions, which include NiCl2, CoCl2, and DMOG, an inhibitor of 2-oxoglutarate-dependent enzymes, also selectively inhibited TNF-α-induced TSLP expression. These results suggested that inactivation of prolyl hydroxylase by hypoxia and hypoxia-mimicking conditions is involved in the repression of TNF-α-induced TSLP expression. Interestingly, the inhibition of TSLP production by hypoxic treatment was significantly reversed by treatment with the HIF-2α antagonist but not with the HIF-1α inhibitor. DMOG-induced inhibition of TSLP promoter activity was dependent on the -71 to +185 bp promoter region, suggesting that the binding of HIF-2 to hypoxia response element (HRE) in this region repressed the TSLP expression. These results indicated that hypoxia and hypoxia-mimicking conditions inhibited TSLP expression via HIF-2 and HRE-dependent mechanisms. Therefore, PHD and HIF-2α could be a new strategy for treatment of atopic dermatitis and psoriasis.

Klíčová slova:

Epidermis – Hypoxia – Inflammation – Luciferase – Medical hypoxia – Oxygen – Promoter regions – Keratinocytes


Zdroje

1. He R, Geha RS. Thymic stromal lymphopoietin. Ann N Y Acad Sci. 2010; 1183: 13–24. doi: 10.1111/j.1749-6632.2009.05128.x 20146705

2. Omori-Miyake M, Ziegler SF. Mouse models of allergic diseases: TSLP and its functional roles. Allergol Int. 2012; 61: 27–34. doi: 10.2332/allergolint.11-RAI-0374 22270069

3. Zhou B, Comeau MR, De Smedt T, Liggitt HD, Dahl ME, Lewis DB, et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol. 2005; 6: 1047–53. doi: 10.1038/ni1247 16142237

4. Segawa R, Shigeeda K, Hatayama T, Dong J, Mizuno N, Moriya T, et al. EGFR transactivation is involved in TNF-α-induced expression of thymic stromal lymphopoietin in human keratinocyte cell line. J Dermatol Sci. 2018; 89: 290–298. doi: 10.1016/j.jdermsci.2017.12.008 29279286

5. Segawa R, Hirasawa N. Exacerbation of allergic diseases by chemicals: role of TSLP. J Pharmacol Sci. 2014; 124: 301–6. doi: 10.1254/jphs.13r16cp 24599138

6. Tsilingiri K, Fornasa G, Rescigno M. Thymic Stromal Lymphopoietin: To Cut a Long Story Short. Cell Mol Gastroenterol Hepatol. 2017; 3: 174–182. doi: 10.1016/j.jcmgh.2017.01.005 28275684

7. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci U S A. 2006; 103: 11736–41. doi: 10.1073/pnas.0604575103 16880407

8. Hatayama T, Segawa R, Mizuno N, Eguchi S, Akamatsu H, Fukuda M, et al. All-Trans Retinoic Acid Enhances Antibody Production by Inducing the Expression of Thymic Stromal Lymphopoietin Protein. J Immunol. 2018; 200: 2670–2676. doi: 10.4049/jimmunol.1701276 29500243

9. Evans SM, Schrlau AE, Chalian AA, Zhang P, Koch CJ. Oxygen levels in normal and previously irradiated human skin as assessed by EF5 binding. J Invest Dermatol. 2006; 126: 2596–606. doi: 10.1038/sj.jid.5700451 16810299

10. O'Shaughnessy RFL, Brown SJ. Insight from the air-skin interface. J Invest Dermatol. 2015; 135: 331–333. doi: 10.1038/jid.2014.457 25573043

11. Befani C, Mylonis I, Gkotinakou IM, Georgoulias P, Hu CJ, Simos G, et al. Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells. Int J Biochem Cell Biol. 2013; 45: 2359–68. doi: 10.1016/j.biocel.2013.07.025 23958427

12. Wong WJ, Richardson T, Seykora JT, Cotsarelis G, Simon MC. Hypoxia-inducible factors regulate filaggrin expression and epidermal barrier function. J Invest Dermatol. 2015; 135: 454–461. doi: 10.1038/jid.2014.283 24999590

13. Cui XY, Tinholt M, Stavik B, Dahm AE, Kanse S, Jin Y, et al. Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer. J Thromb Haemost. 2016; 14: 387–96. doi: 10.1111/jth.13206 26598923

14. Cui XY, Skretting G, Tinholt M, Stavik B, Dahm AEA, Sahlberg KK, et al. A novel hypoxia response element regulates oxygen-related repression of tissue factor pathway inhibitor in the breast cancer cell line MCF-7. Thromb Res. 2017; 157: 111–116. doi: 10.1016/j.thromres.2017.07.013 28734156

15. Manresa MC, Smith L, Casals-Diaz L, Fagundes RR, Brown E, Radhakrishnan P, et al. Pharmacologic inhibition of hypoxia-inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis. Allergy. 2019; 74: 753–766. doi: 10.1111/all.13655 30394557

16. Salnikow K, Donald SP, Bruick RK, Zhitkovich A, Phang JM, Kasprzak KS. Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J Biol Chem. 2004; 279: 40337–44. doi: 10.1074/jbc.M403057200 15271983

17. Harada M, Hirota T, Jodo AI, Hitomi Y, Sakashita M, Tsunoda T. Thymic stromal lymphopoietin gene promoter polymorphisms are associated with susceptibility to bronchial asthma. Am J Respir Cell Mol Biol. 2011; 44: 787–93. doi: 10.1165/rcmb.2009-0418OC 20656951

18. Redhu NS, Saleh A, Halayko AJ, Ali AS, Gounni AS. Essential role of NF-κB and AP-1 transcription factors in TNF-α-induced TSLP expression in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2011; 300: L479–85. doi: 10.1152/ajplung.00301.2009 21148792

19. Cultrone A, de Wouters T, Lakhdari O, Kelly D, Mulder I, Logan E, et al. The NF-κB binding site located in the proximal region of the TSLP promoter is critical for TSLP modulation in human intestinal epithelial cells. Eur J Immunol. 2013; 43: 1053–62. doi: 10.1002/eji.201142340 23310954

20. Cho YS, Bae JM, Chun YS, Chung JH, Jeon YK, Kim IS, et al. HIF-1alpha controls keratinocyte proliferation by up-regulating p21(WAF1/Cip1). Biochim Biophys Acta. 2008; 1783: 323–33. doi: 10.1016/j.bbamcr.2007.11.017 18166158

21. Zhao J, Du F, Shen G, Zheng F, Xu B. The role of hypoxia-inducible factor-2 in digestive system cancers. Cell Death Dis. 2015; 6: e1600. doi: 10.1038/cddis.2014.565 25590810

22. Hindryckx P, De Vos M, Jacques P, Ferdinande L, Peeters H, Olievier K, et al. Hydroxylase inhibition abrogates TNF-alpha-induced intestinal epithelial damage by hypoxia-inducible factor-1-dependent repression of FADD. J Immunol. 2010; 185: 6306–16. doi: 10.4049/jimmunol.1002541 20943999

23. Zheng W, Kuhlicke J, Jäckel K, Eltzschig HK, Singh A, Sjöblom M, et al. Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium. FASEB J. 2009; 23: 204–13. doi: 10.1096/fj.08-110221 18779379

24. Morote-Garcia JC, Rosenberger P, Nivillac NM, Coe IR, Eltzschig HK. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology. 2009; 136: 607–18. doi: 10.1053/j.gastro.2008.10.037 19105964

25. Stavik B, Espada S, Cui XY, Iversen N, Holm S, Mowinkel MC, et al. EPAS1/HIF-2 alpha-mediated downregulation of tissue factor pathway inhibitor leads to a pro-thrombotic potential in endothelial cells. 2016; 1862: 670–678. doi: 10.1016/j.bbadis.2016.01.017 26826018

26. Kim BE, Howell MD, Guttman-Yassky E, Gilleaudeau PM, Cardinale IR, Boguniewicz M. TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier. J Invest Dermatol. 2011; 131: 1272–9. doi: 10.1038/jid.2011.24 21346775


Článek vyšel v časopise

PLOS One


2019 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#