Abstract
Exposure to ultraviolet (UV) irradiation has detrimental effects on skin accompanied by the increased metabolism of hyaluronan (HA), a linear polysaccharide important for the normal physiological functions of skin. In this study, the modulation of human keratinocyte response to UVB irradiation by HA (970 kDa) was investigated. Immortalized human keratinocytes (HaCaT) were irradiated by a single dose of UVB and immediately treated with HA for 6 and 24 h. The irradiation induced a significant decrease in the gene expression of CD44 and toll-like receptor 2 6 h after irradiation. The expressions of other HA receptors, including toll-like receptor 4 and the receptor for HA-mediated motility, were not detected in either the control or UVB-irradiated or HA-treated HaCaT cells. UVB irradiation induced a significant decrease in the gene expression of HA synthase-2 and hyaluronidase-2 6 h after irradiation. The expressions of HA synthase-3 and hyaluronidase-3 were not significantly modulated by UV irradiation. Interestingly, HA treatment did not significantly modulate any of these effects. In contrast, HA significantly suppressed UVB-induced pro-inflammatory cytokine release including interleukin-6 and interleukin-8. Similarly, HA treatment reduced the UVB-mediated production of transforming growth factor β1. HA treatment also significantly reduced the UV irradiation-mediated release of soluble CD44 into the media. Finally, HA partially, but significantly, suppressed the UVB-induced decrease in cell viability. Data indicate that HA had significant protective effects for HaCaT cells against UVB irradiation.
Similar content being viewed by others
References
Averbeck M, Gebhardt CA, Voigt S, Beilharz S, Anderegg U, Termeer CC, Sleeman JP, Simon JC (2007) Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. J Invest Dermatol 127(3):687–697
Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106(3):761–771
Calikoglu E, Sorg O, Tran C, Grand D, Carraux P, Saurat JH, Kaya G (2006) UVA and UVB decrease the expression of CD44 and hyaluronate in mouse epidermis, which is counteracted by topical retinoids. Photochem Photobiol 82(5):1342–1347
Cichy J, Pure E (2003) The liberation of CD44. J Cell Biol 161(5):839–843
Cichy J, Pure E (2004) Cytokines regulate the affinity of soluble CD44 for hyaluronan. FEBS Lett 556(1–3):69–74
Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J, Fischer JW (2007) Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 171(5):1451–1461
Debacq-Chainiaux F, Borlon C, Pascal T, Royer V, Eliaers F, Ninane N, Carrard G, Friguet B, de Longueville F, Boffe S, Remacle J, Toussaint O (2005) Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway. J Cell Sci 118(Pt 4):743–758
Frankova J, Kubala L, Velebny V, Ciz M, Lojek A (2006) The effect of hyaluronan combined with KI3 complex (Hyiodine wound dressing) on keratinocytes and immune cells. J Mater Sci Mater Med 17(10):891–898
Ichihashi M, Ueda M, Budiyanto A, Bito T, Oka M, Fukunaga M, Tsuru K, Horikawa T (2003) UV-induced skin damage. Toxicology 189(1–2):21–39
Jiang D, Liang J, Noble PW (2007) Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol 23:435–461
Kakizaki I, Itano N, Kimata K, Hanada K, Kon A, Yamaguchi M, Takahashi T, Takagaki K (2008) Up-regulation of hyaluronan synthase genes in cultured human epidermal keratinocytes by UVB irradiation. Arch Biochem Biophys 471(1):85–93
Kolarova H, Bino L, Pejchalova K, Kubala L (2010) The expression of NADPH oxidases and production of reactive oxygen species by human lung adenocarcinoma epithelial cell line a549. Folia Biol (Praha) 56(5):211–217
Krejcova D, Pekarova M, Safrankova B, Kubala L (2009) The effect of different molecular weight hyaluronan on macrophage physiology. Neuro Endocrinol Lett 30(Suppl 1):106–111
Margelin D, Fourtanier A, Thevenin T, Medaisko C, Breton M, Picard J (1993) Alterations of proteoglycans in ultraviolet-irradiated skin. Photochem Photobiol 58(2):211–218
Margelin D, Medaisko C, Lombard D, Picard J, Fourtanier A (1996) Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin. J Invest Dermatol 106(3):505–509
Mitani H, Koshiishi I, Toyoda H, Toida T, Imanari T (1999) Alterations of hairless mouse skin exposed to chronic UV irradiation and its prevention by hydrocortisone. Photochem Photobiol 69(1):41–46
Nichols JA, Katiyar SK (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302(2):71–83
Pauloin T, Dutot M, Joly F, Warnet JM, Rat P (2009) High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells. Mol Vis 15:577–583
Quan T, He T, Kang S, Voorhees JJ, Fisher GJ (2002) Ultraviolet irradiation alters transforming growth factor beta/smad pathway in human skin in vivo. J Invest Dermatol 119(2):499–506
Ruszova E, Pavek S, Hajkova V, Jandova S, Velebny V, Papezikova I, Kubala L (2008) Photoprotective effects of glucomannan isolated from Candida utilis. Carbohydr Res 343(3):501–511
Safrankova B, Gajdova S, Kubala L (2010) The potency of hyaluronan of different molecular weights in the stimulation of blood phagocytes. Med Inflam, article ID 380948. doi:10.1155/2010/380948
Stern R, Kogan G, Jedrzejas MJ, Soltes L (2007) The many ways to cleave hyaluronan. Biotechnol Adv 25(6):537–557
Sudel KM, Venzke K, Mielke H, Breitenbach U, Mundt C, Jaspers S, Koop U, Sauermann K, Knussman-Hartig E, Moll I, Gercken G, Young AR, Stab F, Wenck H, Gallinat S (2005) Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol 81(3):581–587
Takahashi Y, Ishikawa O, Okada K, Kojima Y, Igarashi Y, Miyachi Y (1996) Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun-protected skin of aged people. J Dermatol Sci 11(2):129–133
Tsoureli-Nikita E, Watson RE, Griffiths CE (2006) Photoageing: the darker side of the sun. Photochem Photobiol Sci 5(2):160–164
Tzellos TG, Klagas I, Vahtsevanos K, Triaridis S, Printza A, Kyrgidis A, Karakiulakis G, Zouboulis CC, Papakonstantinou E (2009) Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes. Exp Dermatol 18(12):1028–1035
Vistejnova L, Dvorakova J, Hasova M, Muthny T, Velebny V, Soucek K, Kubala L (2009) The comparison of impedance-based method of cell proliferation monitoring with commonly used metabolic-based techniques. Neuro Endocrinol Lett 30(Suppl 1):121–127
Yoneda M, Yamagata M, Suzuki S, Kimata K (1988) Hyaluronic acid modulates proliferation of mouse dermal fibroblasts in culture. J Cell Sci 90(Pt 2):265–273
Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H (2008) Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int 32(11):1405–1411
Acknowledgments
The study was partly supported by grant No. 305/08/1704 from the Czech Science Foundation and research plans AV0Z50040507 and AV0Z50040702. The authors would like to thank J. Stejskalova, K. Becickova and M. Felgrova for their technical assistance with cell cultivation and protein assays.
Conflict of interest
Drs. Hasova, Dvorakova, and Muthny are Contipro Group employees; Dr. Velebny is a Contipro Group employee and stockholder.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hašová, M., Crhák, T., Šafránková, B. et al. Hyaluronan minimizes effects of UV irradiation on human keratinocytes. Arch Dermatol Res 303, 277–284 (2011). https://doi.org/10.1007/s00403-011-1146-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-011-1146-8