Skip to main content

Advertisement

Log in

Comparison of stress-induced PRINS gene expression in normal human keratinocytes and HaCaT cells

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

Abstract

Psoriasis is a chronic inflammatory skin disease that affects approximately 2–4% of the population. We recently described a novel non-coding RNA, psoriasis susceptibility related RNA gene induced by stress (PRINS), that was overexpressed in non-lesional psoriatic epidermis, and its expression was induced by various stress factors such as serum starvation, contact inhibition, ultraviolet (UV)-B irradiation, viral infection and translational inhibition in HaCaT cells. In the present work we set out to compare the stress and microbial agent-induced PRINS expression in normal human keratinocytes (NHKs) and HaCaT cells. Since nuclear factor-κB (NF-κB) is involved in the cellular stress response, we sought to explore whether there is a connection between the NF-κB and PRINS-mediated signal transduction pathways in NHKs and HaCaT cells. We found that the PRINS expression responded differentially to various stress signals and microbial agents in HaCaT cells and in NHKs: after translational inhibition and UV-B treatment, similar induction of PRINS expression occurred with different time courses while after microbial agent treatment, the PRINS expression was significantly induced in HaCaT cells, whereas we could not detect similar changes in NHKs. To explore whether the known NF-κB abnormalities in HaCaT cells could be related to this differential PRINS expression, we silenced the PRINS gene expression with small interfering RNA (siRNA) in both HaCaT cells and in NHKs and monitored NF-κB signal transduction after lipopolysaccharide (LPS) treatment. Silencing of PRINS had no effect on LPS-induced NF-κB activity either in HaCaT cells or in NHKs. Our results indicate that PRINS probably affects keratinocytes functions independently of NF-κB signalling.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bell S, Degitz K, Quirling M, Jilg N, Page S, Brand K (2003) Involvement of nf-kappab signalling in skin physiology and disease. Cell Signal 15(1):1–7

    Article  PubMed  CAS  Google Scholar 

  2. Bender K, Gottlicher M, Whiteside S, Rahmsdorf HJ, Herrlich P (1998) Sequential DNA damage-independent and -dependent activation of nf-kappab by uv. EMBO J 17(17):5170–5181

    Article  PubMed  CAS  Google Scholar 

  3. Bhalerao J, Bowcock AM (1998) The genetics of psoriasis: a complex disorder of the skin and immune system. Hum Mol Genet 7(10):1537–1545

    Article  PubMed  CAS  Google Scholar 

  4. Bos JD, Hulsebosch HJ, Krieg SR, Bakker PM, Cormane RH (1983) Immunocompetent cells in psoriasis in situ immunophenotyping by monoclonal antibodies. Arch Dermatol Res 275(3):181–189

    Article  PubMed  CAS  Google Scholar 

  5. Chaturvedi V, Qin JZ, Denning MF, Choubey D, Diaz MO, Nickoloff BJ (2001) Abnormal nf-kappab signaling pathway with enhanced susceptibility to apoptosis in immortalized keratinocytes. J Dermatol Sci 26(1):67–78

    Article  PubMed  CAS  Google Scholar 

  6. Cheriyath V, Leaman DW, Borden EC (2010) Emerging roles of fam14 family members (g1p3/isg 6–16 and isg12/ifi27) in innate immunity and cancer. J Interferon Cytokine Res 31(1):173–181

    Article  PubMed  Google Scholar 

  7. Collins LJ, Penny D (2009) The rna infrastructure: dark matter of the eukaryotic cell? Trends Genet 25(3):120–128

    Article  PubMed  CAS  Google Scholar 

  8. Duffin KC, Chandran V, Gladman DD, Krueger GG, Elder JT, Rahman P (2008) Genetics of psoriasis and psoriatic arthritis: update and future direction. J Rheumatol 35(7):1449–1453

    PubMed  CAS  Google Scholar 

  9. Ghosh S, Karin M (2002) Missing pieces in the nf-kappab puzzle. Cell 109(Suppl):S81–S96

    Article  PubMed  CAS  Google Scholar 

  10. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: toll-like receptor 4 (tlr4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for tlr4 as the lps gene product. J Immunol 162(7):3749–3752

    PubMed  CAS  Google Scholar 

  11. Kis K, Bodai L, Polyanka H, Eder K, Pivarcsi A, Duda E, Soos G, Bata-Csorgo Z, Kemeny L (2006) Budesonide, but not tacrolimus, affects the immune functions of normal human keratinocytes. Int Immunopharmacol 6(3):358–368

    Article  PubMed  CAS  Google Scholar 

  12. Lewis DA, Hengeltraub SF, Gao FC, Leivant MA, Spandau DF (2006) Aberrant nf-kappab activity in hacat cells alters their response to uv-b signaling. J Invest Dermatol 126(8):1885–1892

    Article  PubMed  CAS  Google Scholar 

  13. Li N, Karin M (1998) Ionizing radiation and short wavelength uv activate nf-kappab through two distinct mechanisms. Proc Natl Acad Sci 95(22):13012–13017

    Article  PubMed  CAS  Google Scholar 

  14. Maas-Szabowski N, Starker A, Fusenig NE (2003) Epidermal tissue regeneration and stromal interaction in hacat cells is initiated by tgf-alpha. J Cell Sci 116(Pt 14):2937–2948

    Article  PubMed  CAS  Google Scholar 

  15. Mercurio F, Young DB, Manning AM (2000) Detection and purification of a multiprotein kinase complex from mammalian cells. Ikk signalsome. Methods Mol Biol 99:109–125

    PubMed  CAS  Google Scholar 

  16. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR (2009) Genome-wide scan reveals association of psoriasis with il-23 and nf-kappab pathways. Nat Genet 41(2):199–204

    Article  PubMed  CAS  Google Scholar 

  17. Olaru F, Jensen LE (2010) Chemokine expression by human keratinocyte cell lines after activation of toll-like receptors. Exp Dermatol 19(8):e314–e316

    Article  PubMed  Google Scholar 

  18. Pivarcsi A, Bodai L, Rethi B, Kenderessy-Szabo A, Koreck A, Szell M, Beer Z, Bata-Csorgoo Z, Magocsi M, Rajnavolgyi E, Dobozy A, Kemeny L (2003) Expression and function of toll-like receptors 2 and 4 in human keratinocytes. Int Immunol 15(6):721–730

    Article  PubMed  CAS  Google Scholar 

  19. Pivarcsi A, Szell M, Kemeny L, Dobozy A, Bata-Csorgo Z (2001) Serum factors regulate the expression of the proliferation-related genes alpha5 integrin and keratin 1, but not keratin 10, in hacat keratinocytes. Arch Dermatol Res 293(4):206–213

    Article  PubMed  CAS  Google Scholar 

  20. Sagoo GS, Cork MJ, Patel R, Tazi-Ahnini R (2004) Genome-wide studies of psoriasis susceptibility loci: a review. J Dermatol Sci 35(3):171–179

    Article  PubMed  CAS  Google Scholar 

  21. Schneider RJ, Mohr I (2003) Translation initiation and viral tricks. Trends Biochem Sci 28(3):130–136

    Article  PubMed  CAS  Google Scholar 

  22. Seitz CS, Lin Q, Deng H, Khavari PA (1998) Alterations in nf-kappab function in transgenic epithelial tissue demonstrate a growth inhibitory role for nf-kappab. Proc Natl Acad Sci 95(5):2307–2312

    Article  PubMed  CAS  Google Scholar 

  23. Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A, Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L, Szell M (2005) Identification and characterization of a novel, psoriasis susceptibility-related non-coding RNA gene, PRINS. J Biol Chem 280(25):24159–24167

    Article  PubMed  CAS  Google Scholar 

  24. Sur I, Ulvmar M, Toftgard R (2008) The two-faced nf-kappab in the skin. Int Rev Immunol 27(4):205–223

    Article  PubMed  CAS  Google Scholar 

  25. Szegedi K, Sonkoly E, Nagy N, Nemeth IB, Bata-Csorgo Z, Kemeny L, Dobozy A, Szell M (2010) The anti-apoptotic protein g1p3 is overexpressed in psoriasis and regulated by the non-coding RNA, PRINS. Exp Dermatol 19(3):269–278

    Article  PubMed  CAS  Google Scholar 

  26. Szell M, Bata-Csorgo Z, Kemeny L (2008) The enigmatic world of mrna-like ncrnas: Their role in human evolution and in human diseases. Semin Cancer Biol 18(2):141–148

    Article  PubMed  CAS  Google Scholar 

  27. Terui T, Ozawa M, Tagami H (2000) Role of neutrophils in induction of acute inflammation in t-cell-mediated immune dermatosis, psoriasis: A neutrophil-associated inflammation-boosting loop. Exp Dermatol 9(1):1–10

    Article  PubMed  CAS  Google Scholar 

  28. Underhill DM, Ozinsky A, Hajjar AM, Stevens A, Wilson CB, Bassetti M, Aderem A (1999) The toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401(6755):811–815

    Article  PubMed  CAS  Google Scholar 

  29. Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM (1996) Suppression of tnf-alpha-induced apoptosis by nf-kappab. Science 274(5288):787–789

    Article  PubMed  Google Scholar 

  30. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D (1999) Cutting edge: Recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J Immunol 163(1):1–5

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by OTKA (NK77434), TÁMOP-4.2.1/B-09/1/KONV-2010-0005 and TÁMOP 4.2.2-08/1-2008.0001. We thank N. E. Fusenig (German Cancer Research Center, Heidelberg, Germany) and Zsuzsanna Győrfy (Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary) for providing cell lines and luciferase reporter gene construct used in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarolta Bacsa.

Additional information

Lilla Bari and Sarolta Bacsa contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bari, L., Bacsa, S., Sonkoly, E. et al. Comparison of stress-induced PRINS gene expression in normal human keratinocytes and HaCaT cells. Arch Dermatol Res 303, 745–752 (2011). https://doi.org/10.1007/s00403-011-1162-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-011-1162-8

Keywords

Navigation