DOI QR코드

DOI QR Code

HaCaT Keratinocytes and Primary Epidermal Keratinocytes Have Different Transcriptional Profiles of Cornified Envelope-Associated Genes to T Helper Cell Cytokines

  • Received : 2012.01.19
  • Accepted : 2012.03.06
  • Published : 2012.03.31

Abstract

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.

Keywords

References

  1. Bassiouny, D. A. and Shaker, O. (2011) Role of interleukin-17 in the pathogenesis of vitiligo. Clin. Exp. Dermatol. 36, 292-297. https://doi.org/10.1111/j.1365-2230.2010.03972.x
  2. Boukamp, P., Petrussevska, R. T., Breitkreutz, D., Hornung, J., Markham, A. and Fusenig, N. E. (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J. Cell Biol. 106, 761-771. https://doi.org/10.1083/jcb.106.3.761
  3. Breitkreutz, D., Schoop, V. M., Mirancea, N., Baur, M., Stark, H. J. and Fusenig, N. E. (1998) Epidermal differentiation and basement membrane formation by HaCaT cells in surface transplants. Eur. J. Cell Biol. 75, 273-286. https://doi.org/10.1016/S0171-9335(98)80123-4
  4. Brown, S. J., Kroboth, K., Sandilands, A., Campbell, L. E., Pohler, E., Kezic, S., Cordell, H. J., McLean, W. H. and Irvine, A. D. (2012) Intragenic copy number variation within fi laggrin contributes to the risk of atopic dermatitis with a dose-dependent effect. J. Invest. Dermatol. 132, 98-104. https://doi.org/10.1038/jid.2011.342
  5. Cork, M. J., Danby, S. G., Vasilopoulos, Y., Hadgraft, J., Lane, M. E., Moustafa, M., Guy, R. H., Macgowan, A. L., Tazi-Ahnini, R. and Ward, S. J. (2009) Epidermal barrier dysfunction in atopic dermatitis. J. Invest. Dermatol. 129, 1892-1908. https://doi.org/10.1038/jid.2009.133
  6. Cork, M. J., Robinson, D. A., Vasilopoulos, Y., Ferguson, A., Moustafa, M., MacGowan, A., Duff, G. W., Ward, S. J. and Tazi-Ahnini, R. (2006) New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J. Allergy Clin. Immunol. 118, 3-21. https://doi.org/10.1016/j.jaci.2006.04.042
  7. Grabbe, J., Welker, P., Rosenbach, T., Nürnberg, W., Krüger- Krasagakes, S., Artuc, M., Fiebiger, E. and Henz, B. M. (1996) Release of stem cell factor from a human keratinocyte line, HaCaT, is increased in differentiating versus proliferating cells. J. Invest. Dermatol. 107, 219-224. https://doi.org/10.1111/1523-1747.ep12329664
  8. Guijarro, M. V., Leal, J. F., Fominaya, J., Blanco-Aparicio, C., Alonso, S., Lleonart, M., Castellvi, J., Ruiz, L., Ramon, Y. Cajal, S. and Carnero, A. (2007) MAP17 overexpression is a common characteristic of carcinomas. Carcinogenesis. 28, 1646-1652. https://doi.org/10.1093/carcin/bgm083
  9. Hoffjan, S. and Stemmler, S. (2007) On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. Br. J. Dermatol. 157, 441-449. https://doi.org/10.1111/j.1365-2133.2007.07999.x
  10. Lehmann, B. (1997) HaCaT cell line as a model system for vitamin D3 metabolism in human skin. J. Invest. Dermatol. 108, 78-82. https://doi.org/10.1111/1523-1747.ep12285640
  11. Nickoloff, B. J., Qin, J. Z. and Nestle, F. O. (2007) Immunopathogenesis of psoriasis. Clin. Rev. Allergy Immunol. 33, 45-56. https://doi.org/10.1007/s12016-007-0039-2
  12. Noh, M., Yeo, H., Ko, J., Kim, H. K. and Lee, C. H. (2009) MAP17 is associated with the T-helper cell cytokine-induced down-regulation of fi laggrin transcription in human keratinocytes. Exp. Dermatol. 19, 355-362.
  13. Ou, L. S. and Huang, J. L. (2007) Cellular aspects of atopic dermatitis. Clin. Rev. Allergy Immunol. 33, 191-198. https://doi.org/10.1007/s12016-007-0045-4
  14. Ouyang, W., Kolls, J. K. and Zheng, Y. (2008) The biological functions of T helper 17 cell effector cytokines in infl ammation. Immunity. 28, 454-467. https://doi.org/10.1016/j.immuni.2008.03.004
  15. Pfaffl , M. W., Horgan, G. W. and Dempfl e, L. (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic. Acids. Res. 30, e36. https://doi.org/10.1093/nar/30.9.e36
  16. Proksch, E., Fölster-Holst, R. and Jensen, J. M. (2006) Skin barrier function, epidermal proliferation and differentiation in eczema. J. Dermatol. Sci. 43, 159-169. https://doi.org/10.1016/j.jdermsci.2006.06.003
  17. Ryle, C. M., Breitkreutz, D., Stark, H. J., Leigh, I. M., Steinert, P. M., Roop, D. and Fusenig, N. E. (1989) Density-dependent modulation of synthesis of keratins 1 and 10 in the human keratinocyte line HACAT and in ras-transfected tumorigenic clones. Differentiation. 40, 42-54. https://doi.org/10.1111/j.1432-0436.1989.tb00812.x
  18. Schroder, J. M. and Harder, J. (1999) Human beta-defensin-2. Int. J. Biochem. Cell Biol. 31, 645-651. https://doi.org/10.1016/S1357-2725(99)00013-8

Cited by

  1. Attenuation of UV-B exposure-induced inflammation by abalone hypobranchial gland and gill extracts vol.39, pp.5, 2017, https://doi.org/10.3892/ijmm.2017.2939
  2. Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-02802-0
  3. Prokineticin 2 Plays a Pivotal Role in Psoriasis vol.13, 2016, https://doi.org/10.1016/j.ebiom.2016.10.022
  4. Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-12041-y
  5. Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection vol.10, pp.4, 2015, https://doi.org/10.1371/journal.pone.0124280
  6. Cytotoxic Activity and Structure-Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles vol.13, pp.12, 2018, https://doi.org/10.1002/cmdc.201800075
  7. antimicrobial nanostructures: the key role of organo–inorganic frameworks in tuning eumelanin's biocide action mechanism through membrane interaction vol.8, pp.50, 2018, https://doi.org/10.1039/C8RA04315A
  8. A Differential Innate Immune Response in Active and Chronic Stages of Bovine Infectious Digital Dermatitis vol.9, pp.1664-302X, 2018, https://doi.org/10.3389/fmicb.2018.01586
  9. RNAI-MEDIATED SILENCING OF MATRIX METALLOPROTEINASE 1 IN EPIDERMAL KERATINOCYTES INFLUENCES THE BIOLOGICAL EFFECTS OF INTERLEUKIN 17A vol.22, pp.4, 2012, https://doi.org/10.18699/vj18.378
  10. Threonine 454 phosphorylation in Grainyhead-like 3 is important for its function and regulation by the p38 MAPK pathway vol.1865, pp.7, 2018, https://doi.org/10.1016/j.bbamcr.2018.04.010
  11. Cytotoxicity profiling of deep eutectic solvents to human skin cells vol.9, pp.None, 2012, https://doi.org/10.1038/s41598-019-39910-y
  12. Functional Skin Grafts: Where Biomaterials Meet Stem Cells vol.2019, pp.None, 2012, https://doi.org/10.1155/2019/1286054
  13. Antagonizing Retinoic Acid-Related-Orphan Receptor Gamma Activity Blocks the T Helper 17/Interleukin-17 Pathway Leading to Attenuated Pro-inflammatory Human Keratinocyte and Skin Responses vol.10, pp.None, 2019, https://doi.org/10.3389/fimmu.2019.00577
  14. FGF19 sustains the high proliferative ability of keratinocytes in psoriasis through the regulation of Wnt/GSK‐3β/β‐catenin signalling via FGFR4 vol.46, pp.8, 2012, https://doi.org/10.1111/1440-1681.13103
  15. In Situ Crosslinking Bionanocomposite Hydrogels with Potential for Wound Healing Applications vol.10, pp.4, 2019, https://doi.org/10.3390/jfb10040050
  16. Deep Sequencing MicroRNAs from Extracellular Membrane Vesicles Revealed the Association of the Vesicle Cargo with Cellular Origin vol.21, pp.3, 2012, https://doi.org/10.3390/ijms21031141
  17. Inhibition of keratinocyte necroptosis mediated by RIPK1/RIPK3/MLKL provides a protective effect against psoriatic inflammation vol.11, pp.2, 2020, https://doi.org/10.1038/s41419-020-2328-0
  18. The potential of Salvia officinalis as a suppressor of cell proliferation in animal feed and human nutrition: an experimental study vol.44, pp.2, 2012, https://doi.org/10.3906/vet-1910-23
  19. Repression of miR-142–3p alleviates psoriasis-like inflammation by repressing proliferation and promoting apoptosis of keratinocytes via targeting Sema3A vol.52, pp.None, 2012, https://doi.org/10.1016/j.mcp.2020.101573
  20. Impact of sesquiterpene lactones on the skin and skin-related cells? A systematic review of in vitro and in vivo evidence vol.265, pp.None, 2012, https://doi.org/10.1016/j.lfs.2020.118815
  21. Crataegus laevigata Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways vol.26, pp.4, 2021, https://doi.org/10.3390/molecules26040869
  22. Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract vol.11, pp.3, 2012, https://doi.org/10.1002/2211-5463.13076
  23. The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis vol.13, pp.7, 2012, https://doi.org/10.3390/nu13072178
  24. IL6R is a target of miR‐197 in human keratinocytes vol.30, pp.8, 2012, https://doi.org/10.1111/exd.14169
  25. The Role of Andrographolide on Skin Inflammations and Modulation of Skin Barrier Functions in Human Keratinocyte vol.26, pp.5, 2021, https://doi.org/10.1007/s12257-020-0289-x
  26. The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis vol.22, pp.19, 2012, https://doi.org/10.3390/ijms221910661
  27. Use of Cytokine Mix-, Imiquimod-, and Serum-Induced Monoculture and Lipopolysaccharide- and Interferon Gamma-Treated Co-Culture to Establish In Vitro Psoriasis-like Inflammation Models vol.10, pp.11, 2021, https://doi.org/10.3390/cells10112985
  28. Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery-Starting Points and Recent Developments vol.13, pp.11, 2012, https://doi.org/10.3390/pharmaceutics13111852
  29. A review of diabetic wound models-Novel insights into diabetic foot ulcer vol.15, pp.12, 2012, https://doi.org/10.1002/term.3246
  30. Quorum quenchers affect the virulence regulation of non-mucoid, mucoid and heavily mucoid biofilms co-cultured on cell lines vol.105, pp.23, 2012, https://doi.org/10.1007/s00253-021-11638-8