MRI  Vol.3 No.3 , August 2014
Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin
ABSTRACT

Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.


Cite this paper
Sakura, M. , Chiba, Y. , Kamiya, E. , Furukawa, A. , Kawamura, N. , Niwa, M. , Takeuchi, M. , Enokido, Y. and Hosokawa, M. (2014) Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin. Modern Research in Inflammation, 3, 82-89. doi: 10.4236/mri.2014.33010.
References
[1]   Farage, M.A., Miller, K.W., Elsner, P. and Maibach, H.I. (2008) Intrinsic and Extrinsic Factors in Skin Ageing: A Review. International Journal of Cosmetic Science, 30, 87-95.
http://dx.doi.org/10.1111/j.1468-2494.2007.00415.x

[2]   Kligman, L.H. and Kligman, A.M. (1986) The Nature of Photoaging: Its Prevention and Repair. Photodermatology, 3, 215-227.

[3]   Rabe, J.H., Mamelak, A.J., McElgunn, P.J., Morison, W.L. and Sauder, D.N. (2006) Photoaging: Mechanisms and Repair. Journal of the American Academy of Dermatology, 55, 1-19.
http://dx.doi.org/10.1016/j.jaad.2005.05.010

[4]   Gilchrest, B.A. (1989) Skin Aging and Photoaging: An Overview. Journal of the American Academy of Dermatology, 21, 610-613. http://dx.doi.org/10.1016/S0190-9622(89)70227-9

[5]   Braverman, I.M. and Fonferko, E. (1982) Studies in Cutaneous Aging: I. The Elastic Fiber Network. The Journal of Investigative Dermatology, 78, 434-443.
http://dx.doi.org/10.1111/1523-1747.ep12507866

[6]   Lee, J.Y., Kim, Y.K., Seo, J.Y., et al. (2008) Loss of Elastic Fibers Causes Skin Wrinkles in Sun-Damaged Human Skin. Journal of Dermatological Science, 50, 99-107.
http://dx.doi.org/10.1016/j.jdermsci.2007.11.010

[7]   Mukherjee, S., Date, A., Patravale, V., Korting, H.C., Roeder, A. and Weindl, G. (2006) Retinoids in the Treatment of Skin Aging: An Overview of Clinical Efficacy and Safety. Clinical Interventions in Aging, 1, 327-348.

[8]   Werth, B.B., Bashir, M., Chang, L. and Werth, V.P. (2011) Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin. PLoS One, 6, e14830. http://dx.doi.org/10.1371/journal.pone.0014830

[9]   El-Domyati, M., Attia, S., Saleh, F., et al. (2002) Intrinsic Aging vs. Photoaging: A Comparative Histopathological, Immunohistochemical, and Ultrastructural Study of Skin. Experimental Dermatology, 11, 398-405. http://dx.doi.org/10.1034/j.1600-0625.2002.110502.x

[10]   Naylor, E.C., Watson, R.E. and Sherratt, M.J. (2011) Molecular Aspects of Skin Ageing. Maturitas, 69, 249-256. http://dx.doi.org/10.1016/j.maturitas.2011.04.011

[11]   Yaar, M. and Gilchrest, B.A. (2007) Photoageing: Mechanism, Prevention and Therapy. The British Journal of Dermatology, 157, 874-887. http://dx.doi.org/10.1111/j.1365-2133.2007.08108.x

[12]   Quan, T., Qin, Z., Robichaud, P., Voorhees, J.J. and Fisher, G.J. (2011) CCN1 Contributes to Skin Connective Tissue Aging by Inducing Age-Associated Secretory Phenotype in Human Skin Dermal Fibroblasts. Journal of Cell Communication and Signaling, 5, 201-207.
http://dx.doi.org/10.1007/s12079-011-0144-0

[13]   Varani, J., Warner, R.L., Gharaee-Kermani, M., et al. (2000) Vitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin. The Journal of Investigative Dermatology, 114, 480-486.
http://dx.doi.org/10.1046/j.1523-1747.2000.00902.x

[14]   Fisher, G.J., Kang, S., Varani, J., et al. (2002) Mechanisms of Photoaging and Chronological Skin Aging. Archives of Dermatology, 138, 1462-1470. http://dx.doi.org/10.1001/archderm.138.11.1462

[15]   Kligman, L.H. (1996) The Hairless Mouse Model for Photoaging. Clinics in Dermatology, 14, 183-195. http://dx.doi.org/10.1016/0738-081X(95)00154-8

[16]   Benavides, F., Oberyszyn, T.M., VanBuskirk, A.M., Reeve, V.E. and Kusewitt, D.F. (2009) The Hairless Mouse in Skin Research. Journal of Dermatological Science, 53, 10-18.
http://dx.doi.org/10.1016/j.jdermsci.2008.08.012

[17]   Inomata, S., Matsunaga, Y., Amano, S., et al. (2003) Possible Involvement of Gelatinases in Basement Membrane Damage and Wrinkle Formation in Chronically Ultraviolet B-Exposed Hairless Mouse. The Journal of Investigative Dermatology, 120, 128-134. http://dx.doi.org/10.1046/j.1523-1747.2003.12021.x

[18]   Ropke, C.D., Sawada, T.C., da Silva, V.V., Michalany, N.S. and de Moraes Barros, S.B. (2005) Photoprotective Effect of Pothomorphe umbellata Root Extract against Ultraviolet Radiation Induced Chronic Skin Damage in the Hairless Mouse. Clinical and Experimental Dermatology, 30, 272-276.
http://dx.doi.org/10.1111/j.1365-2230.2005.01749.x

[19]   Kligman, L.H., Mezick, J.A., Capetola, R.J. and Thorne, E.G. (1992) Lifetime Topical Application of Tretinoin to Hairless Mice. Acta Dermato-Venereologica, 72, 418-422.

[20]   Peres, P.S., Terra, V.A., Guarnier, F.A., Cecchini, R. and Cecchini, A.L. (2011) Photoaging and Chronological Aging Profile: Understanding Oxidation of the Skin. Journal of Photochemistry and Photobiology B, Biology, 103, 93-97. http://dx.doi.org/10.1016/j.jphotobiol.2011.01.019

[21]   Sakura, M., Chiba, Y., Kamiya, E., et al. (2013) Spontaneous Occurrence of Photoageing-Like Phenotypes in the Dorsal Skin of Old SAMP1 Mice, an Oxidative Stress Model. Experimental Dermatology, 22, 62-64. http://dx.doi.org/10.1111/exd.12059

[22]   Hosokawa, M. (2002) A Higher Oxidative Status Accelerates Senescence and Aggravates Age-Dependent Disorders in SAMP Strains of Mice. Mechanisms of Ageing and Development, 123, 1553-1561.
http://dx.doi.org/10.1016/S0047-6374(02)00091-X

[23]   Chiba, Y., Yamashita, Y., Ueno, M., et al. (2005) Cultured Murine Dermal Fibroblast-Like Cells from SenescenceAccelerated Mice as in Vitro Models for Higher Oxidative Stress Due to Mitochondrial Alterations. Journal of Gerontology: Series A, Biological Sciences & Medical Sciences, 60, 1087-1098. http://dx.doi.org/10.1093/gerona/60.9.1087

[24]   Chiba, Y., Shimada, A. and Hosokawa, M. (2010) The SAM Strain of Mice, a Higher Oxidative Stress, Age-Dependent Degenerative Disease, and Senescence Acceleration Model. In: Bondy, S.C. and Maiese, K., Eds., Aging and Age-Related Disorders, Oxidative Stress in Applied Basic Research and Clinical Practice, Springer Science + Business Media LLC, New York, 359-380.

[25]   Schwartz, E., Sapadin, A.N. and Kligman, L.H. (1998) Ultraviolet B Radiation Increases Steady-State mRNA Levels for Cytokines and Integrins in Hairless Mouse Skin: Modulation by Topical Tretinoin. Archives of Dermatological Research, 290, 137-144. http://dx.doi.org/10.1007/s004030050279

[26]   Hernandez Cruz, A., Garcia-Jimenez, S., Zucatelli Mendonca, R. and Petricevich, V.L. (2008) Pro- and Anti-Inflammatory Cytokines Release in Mice Injected with Crotalus durissus Terrificus Venom. Mediators of Inflammation, 2008, Article ID: 874962. http://dx.doi.org/10.1155/2008/874962

[27]   Nyati, K.K., Prasad, K.N., Rizwan, A., Verma, A. and Paliwal, V.K. (2011) TH1 and TH2 Response to Campylobacter jejuni Antigen in Guillain-Barre Syndrome. Archives of Neurology, 68, 445-452.
http://dx.doi.org/10.1001/archneurol.2011.51

[28]   Kidd, P. (2003) Th1/Th2 Balance: The Hypothesis, Its Limitations, and Implications for Health and Disease. Alternative Medicine Review, 8, 223-246.

[29]   Asadullah, K., Sterry, W., Stephanek, K., et al. (1998) IL-10 Is a Key Cytokine in Psoriasis. Proof of Principle by IL-10 Therapy: A New Therapeutic Approach. The Journal of Clinical Investigation, 101, 783-794. http://dx.doi.org/10.1172/JCI1476

[30]   Kim, Y.K., Jung, H.G., Myint, A.M., Kim, H. and Park, S.H. (2007) Imbalance between Pro-Inflammatory and Anti-Inflammatory Cytokines in Bipolar Disorder. Journal of Affective Disorders, 104, 91-95.
http://dx.doi.org/10.1016/j.jad.2007.02.018

 
 
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