Skip to main content

Advertisement

SpringerLink
Log in

Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case–control study

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Janus kinases (JAKs) are non-receptor protein tyrosine kinases that are expressed in many tissues. Once the JAKs are activated, a cascade of further signaling events is triggered involving phosphorylation of selected receptor chain tyrosines, binding of signal transducer and activator of transcription (STAT) proteins and phosphorylation of these STATs. Due to their ability to selectively modulate immune function, targeted JAK inhibitors are promising candidates for some skin diseases such as psoriasis and atopic dermatitis. The aim of this study was to assess the level of JAK1 in both vitiligo and psoriasis patients before and after treatment with NB-UVB which is considered a gold standard therapy for both diseases. This study was conducted on 10 patients with psoriasis, 10 patients with vitiligo and 10 controls. JAK1 levels before and after treatment with NB-UVB 311 nm (36 sessions) were measured using Western blot assay. The level of JAK1 was significantly higher in vitiligo and psoriasis patients than controls. There was a decline in the level of JAK1 after treatment, which was statistically significant. VASI and PASI scores of patients decreased after treatment with NB-UVB. In psoriatic patients, the JAK1 level positively correlated with the female participants, disease duration and PASI change. It was concluded that JAK1 plays a role in the pathogenesis of both vitiligo and psoriasis based on its upregulated level before treatment and downregulated level after treatment. This raises the possibility of using the JAK1 inhibitors as targeted immunotherapy for vitiligo and psoriasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CCL:

C-C motif chemokine ligand

CNTF-R:

Ciliary neurotrophic factor-receptor

CXCL:

Chemokine (C-X-C motif) ligand

IFN-R:

Interferon receptor

IL:

Interleukin

JAK:

Janus kinase

LIF-R:

Leukemia inhibitory factor-receptor

NB-UVB:

Narrow band ultraviolet B

NNT-1R/BSF3R:

Novel neurotrophin-1/B cell-stimulating factor-3 receptor

OSM-R/ CT-1R:

Oncostatin M/Cardiotrophin-1-receptor

PASI:

Psoriasis area and severity index

PTK:

Protein tyrosine kinase

STAT:

Signal transducer and activator of transcription

Th17:

T helper17

TNF-α:

Tumor necrosis factor-alpha

TYK:

Tyrosine kinase

VASI:

Vitiligo area and severity index

References

  1. Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296(5573):1653–1655

    Article  CAS  PubMed  Google Scholar 

  2. Andrés RM, Hald A, Johansen C, Kragballe K, Iversen L (2013) Studies of Jak/STAT3 expression and signalling in psoriasis identifies STAT3-Ser727 phosphorylation as a modulator of transcriptional activity. Exp Dermatol 22:323–328. https://doi.org/10.1111/exd.12128

    Article  PubMed  Google Scholar 

  3. Attwa E, Gamil H, Assaf M, Ghonemy S (2012) Over-expression of tumor necrosis factor-α in vitiligo lesions after narrow-band UVB therapy: an immunohistochemical study. Arch Dermatol Res 304:823–830. https://doi.org/10.1007/s00403-012-1269-6

    Article  CAS  PubMed  Google Scholar 

  4. Bach EA, Aguet M, Schreiber RD (1997) The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563–591. https://doi.org/10.1146/annurev.immunol.15.1.563

    Article  CAS  PubMed  Google Scholar 

  5. Basak PY, Adiloglu AK, Koc IG, Tas T, Akkaya VB (2008) Evaluation of activatory and inhibitory natural killer cell receptors in non-segmental vitiligo: a flow cytometric study. J Eur Acad Dermatol Venereol 22:970–976. https://doi.org/10.1111/j.1468-3083.2008.02681.x

    Article  CAS  PubMed  Google Scholar 

  6. Bhise SB, Nalawade AD, Wadhawa H (2004) Role of protein tyrosine kinase inhibitors in cancer therapeutics. Indian J Biochem Biophys 41(6):273–280

    CAS  PubMed  Google Scholar 

  7. Craiglow BG, King BA(2015)Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy. JAMA Dermatol151:1110–1112. https://doi.org/10.1001/jamadermatol.2015.1520

    Article  PubMed  Google Scholar 

  8. Di Lernia V, Bardazzi F (2016) Profile of tofacitinib citrate and its potential in the treatment of moderate-to-severe chronic plaque psoriasis. Drug Des Devel Ther 10:533–539. https://doi.org/10.2147/DDDT.S82599

    Article  PubMed  PubMed Central  Google Scholar 

  9. Elloso MM, Gomez-Angelats M, Fourie AM (2012) Targeting the Th17 pathway in psoriasis. J Leukoc Biol 92:1187–1197. https://doi.org/10.1189/jlb.0212101

    Article  CAS  PubMed  Google Scholar 

  10. Gaffen SL (2009) Structure and signaling in the IL-17 receptor family. Nat Rev Immunol 9(8):556–567. https://doi.org/10.1038/nri2586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Galluzzo M, D’Adamio S, Servoli S, Bianchi L, Chimenti S, Talamonti M (2016) Tofacitinib for the treatment of psoriasis. Expert Opin Pharmacother 17(10):1421–1433. https://doi.org/10.1080/14656566.2016.1195812

    Article  CAS  PubMed  Google Scholar 

  12. Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol Rev 228:273–287. https://doi.org/10.1111/j.1600-065X.2008.00754.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H (2004) Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. Arch Dermatol 140:677–683. https://doi.org/10.1001/archderm.140.6.677

    Article  PubMed  Google Scholar 

  14. Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R, Christiano AM, Mackay-Wiggan J (2016) Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol 74(2):370–371. https://doi.org/10.1016/j.jaad.2015.09.073

    Article  PubMed  Google Scholar 

  15. Hsu L, Armstrong AW (2014) JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res 2014: 283617. https://doi.org/10.1155/2014/283617

  16. Ishizaki M, Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, Maeda H, Shimoda K, Oritani K, Matsuda T (2011) Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J Immunol 187:181–189. https://doi.org/10.4049/jimmunol.1003244

    Article  CAS  PubMed  Google Scholar 

  17. Klarquist J, Denman CJ, Hernandez C, Wainwright DA, Strickland FM, Overbeck A, Mehrotra S, Nishimura MI, Le Poole IC (2010) Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res 23:276–286. https://doi.org/10.1111/j.1755-148X.2010.00688.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kofoed K, Skov L, Zachariae C (2015) New drugs and treatment targets in psoriasis. Acta Derm Venereol 95(2):133–139. https://doi.org/10.2340/00015555-1931

    Article  PubMed  Google Scholar 

  19. Kwatra SG, Dabade TS, Gustafson CJ, Feldman SR (2012) JAK inhibitors in psoriasis: a promising new treatment modality. J Drugs Dermatol 11(8):913–918

    CAS  PubMed  Google Scholar 

  20. Lai SY, Johnson FM (2010) Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Update 13:67–78. https://doi.org/10.1016/j.drup.2010.04.001

    Article  CAS  Google Scholar 

  21. Landry DA, Sormany F, Haché J, Roumaud P, Martin LJ (2017) Steroidogenic genes expressions are repressed by high levels of leptin and the JAK/STAT signaling pathway in MA-10 Leydig cells. Mol Cell Biochem. https://doi.org/10.1007/s11010-017-3017-x

    PubMed  Google Scholar 

  22. Ludbrook VJ, Hicks KJ, Hanrott KE, Patel JS, Binks MH, Wyres MR, Watson J, Wilson P, Simeoni M, Schifano LA, Reich K, Griffiths CE (2016) Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study. Br J Dermatol 174:985–995. https://doi.org/10.1111/bjd.14399

    Article  CAS  PubMed  Google Scholar 

  23. Marks R, Barton SP, Shuttleworth D, Finlay AY (1989) Assessment of disease progress in psoriasis. Arch Dermatol 125:235–240. https://doi.org/10.1001/archderm.1989.01670140087017

    Article  CAS  PubMed  Google Scholar 

  24. Ortiz-Ibáñez K, Alsina MM, Muñoz-Santos C (2013) Tofacitinib and other kinase inhibitors in the treatment of psoriasis. Actas Dermosifiligor 104:304–310. https://doi.org/10.1016/j.adengl.2013.03.002

    Article  Google Scholar 

  25. Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, Macias W, Zhang X, Janes JM (2016) A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol 174(6):1266–1276. https://doi.org/10.1111/bjd.14403

    Article  CAS  PubMed  Google Scholar 

  26. Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, Levy R, Williams W, Gottlieb A (2012) Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 67(4):658–64. https://doi.org/10.1016/j.jaad.2011.12.018

    Article  Google Scholar 

  27. Rane SG, Reddy EP (2000) Janus kinases: components of multiple signaling pathways. Oncogene 19:5662–5679. https://doi.org/10.1038/sj.onc.1203925

    Article  CAS  PubMed  Google Scholar 

  28. Schindler C, Plumlee C (2008) Inteferons pen the JAK-STAT pathway. Semin Cell Dev Biol 19:311–318. https://doi.org/10.1016/j.semcdb.2008.08.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nasr Seif El, Shaker H, Fawzi OG, El-Hanafi MM G (2013) Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets. J Eur Acad Dermatol Venereol 27:103–108. https://doi.org/10.1111/j.1468-3083.2011.04368.x

    Article  Google Scholar 

  30. Sohn SJ, Barrett K, Van Abbema A, Chang C, Kohli PB, Kanda H, Smith J, Lai Y, Zhou A, Zhang B, Yang W et al (2013) A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors. J Immunol 191:2205–2216. https://doi.org/10.4049/jimmunol.1202859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. van den Boorn JG, Konijnenberg D, Dellemijn TA, van der Veen JP, Bos JD, Melief CJ, Vyth-Dreese FA, Luiten RM (2009) Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 129:2220–2232. https://doi.org/10.1038/jid.2009.32

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Hanan Rabea Nada, Dina Ahmed El Sharkawy & Maha Fathy Elmasry

  2. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Laila Ahmed Rashed

  3. Cairo, Egypt

    Sally Mamdouh

Authors
  1. Hanan Rabea Nada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dina Ahmed El Sharkawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maha Fathy Elmasry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laila Ahmed Rashed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sally Mamdouh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maha Fathy Elmasry.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflicts of interest.

Funding

The authors did not receive any external funding for this work.

Ethical approval

All procedures performed in the study were in accordance to the ethical standards of the Dermatology Research Ethical Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

A written informed consent was obtained from each patient for the participation in the study and photography.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nada, H.R., El Sharkawy, D.A., Elmasry, M.F. et al. Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case–control study. Arch Dermatol Res 310, 39–46 (2018). https://doi.org/10.1007/s00403-017-1792-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-017-1792-6

Keywords

Search

Navigation