Abstract
Local hyperthermia has been successfully used in the treatment of viral warts. However, the mechanism of action of hyperthermia has largely remained unclear. In this study we evaluated the effect of local hyperthermia on the induction of apoptosis in human keratinocytes, and expression of apoptosis-related genes in both condyloma acuminata (CA) and normal skin. The study showed that higher hyperthermia increased the number of apoptotic keratinocytes in CA and normal skin. The temperature-dependent increased expression of Fas and Bax were observed in both CA and normal skin. In contrast, the expression of Bcl-2 in CA was decreased at both transcriptional and translational levels. Furthermore, the transcriptional expression of DR4 and DR5 were increased in a temperature-dependent manner in CA, but not in normal skin. These results suggest that different mechanisms of action might be involved in hyperthermia induced apoptosis in CA and normal skin.
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Abbreviations
- CA:
-
Condyloma acuminata
- HPV:
-
Human papillomavirus
- TNF:
-
Tumor necrosis factor
- OPG:
-
Osteoprotegerin
- DD:
-
Death domains
- DR:
-
Death receptor
- PBS:
-
Phosphate buffered solution
- TRAIL:
-
Tumor necrosis factor-related apoptosis-inducing ligand
- TUNEL:
-
Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
- IHC:
-
Immunohistochemistry
References
Koutsky L (1997) Epidemiology of genital human papillomavirus infection. Am J Med 102:3–8. doi:10.1016/S0002-9343(97)00177-0
Maw RD, Reitano M, Roy M (1998) An international survey of patients with genital warts: perceptions regarding treatment and impact on lifestyle. Int J STD AIDS 9:571–578. doi:10.1258/0956462981921143
Kodner CM, Nasraty S (2004) Management of genital warts. Am Fam Physician 70:2335–2342
Wust P, Hildebrandt B (2002) Hyperthermia in combined treatment of cancer. Lancet Oncol 3:487–497. doi:10.1016/S1470-2045(02)00818-5
Harmon BV, Corder AM, Collins RJ et al (1990) Cell death induced in a murine mastocytoma by 42–47°C heating in vitro: evidence that the form of death changes from apoptosis to necrosis above a critical heat load. Int J Radiat Biol 58:845–858. doi:10.1080/09553009014552221
Sakaguchi Y, Stephens LC, Makino M et al (1995) Apoptosis in tumors and normal tissues induced by whole body hyperthermia in rats. Cancer Res 55:5459–5464
Stern P, Levine N (1992) Controlled localized heat therapy in cutaneous warts. Arch Dermatol 128(7):945–948. doi:10.1001/archderm.128.7.945
Pfau A, Abd-el-Raheem TA, Baumler W et al (1994) Nd:YAG laser hyperthermia in the treatment of recalcitrant verrucae vulgares (Regensburg’s technique). Acta Derm Venereol 74(3):212–214
El-Tonsy MH, Anbar TE, El-Domyati M et al (1999) Density of viral particles in pre and post Nd: YAG laser hyperthermia therapy and cryotherapy in plantar warts. Int J Dermatol 38(5):393–398. doi:10.1046/j.1365-4362.1999.00719.x
Werness BA, Levine AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248:76–79. doi:10.1126/science.2157286
Garnett T, Filippova M, Duerksen-Hughes PJ (2006) Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. Cell Death Differ 13(11):1915–1926. doi:10.1038/sj.cdd.4401886
Filippova M, Parkhurst L, Duerksen-Hughes PJ (2004) The human papillomavirus 16 E6 protein binds to Fas associated death domain and protects from Fas-triggered apoptosis. J Biol Chem 279:25729–25744. doi:10.1074/jbc.M401172200
Kabsch K, Mossadegh N, Kohl A et al (2004) The HPV-16 E5 protein inhibits TRAIL- and FasL-mediated apoptosis in human keratinocyte raft cultures. Intervirology 47:48–56. doi:10.1159/000076642
Kabsch K, Alonso A (2002) The human papillomavirus type 16 E5 protein impairs TRAIL- and FasL mediated apoptosis in HaCaT cells by different mechanisms. J Virol 76:12162–12172. doi:10.1128/JVI.76.23.12162-12172.2002
Sima N, Wang W, Kong D et al (2008) RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression in cervical cancer cells and apoptosis via upregulation of Rb and p53. Apoptosis 13(2):273–281. doi:10.1007/s10495-007-0163-8
Singh M, Singh N (2008) Induction of apoptosis by hydrogen peroxide in HPV 16 positive human cervical cancer cells: involvement of mitochondrial pathway. Mol Cell Biochem 310(1–2):57–65. doi:10.1007/s11010-007-9665-5
Tjalma WA, Weyler JJ, Bogers JJ et al (2001) The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol 97:223–230. doi:10.1016/S0301-2115(00)00541-8
Wiley SR, Schooley K, Smolak PJ et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682. doi:10.1016/1074-7613(95)90057-8
Pan G, Rourke KO, Chinnaiyan AM et al (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111–113. doi:10.1126/science.276.5309.111
Ostberg JR, Kabingu E, Repasky EA (2003) Thermal regulation of dendritic cell activation and migration from skin explants. Int J Hyperthermia 19:520–533. doi:10.1080/02656730310001607986
Van den Brule AJ, Meijer CJ, Bakels V et al (1990) Rapid detection of human papillomavirus in cervical scrapes by combined general primer-mediated and type-specific polymerase chain reaction. J Clin Microbiol 28(12):2739–2743
Ni X, Hazarika P, Zhang C et al (2001) Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8 + cytotoxic T lymphocytes in mycosis fungoides: a potential mechanism of tumor immune escape? Clin Cancer Res 7(9):2682–2692
Hildebrandt B, Hegewisch-Becker S, Kerner T et al (2005) Current status of radiant whole-body hyperthermia at temperatures >41.5 degrees C and practical guidelines for the treatment of adults. The German interdisciplinary working group on hyperthermia. Int J Hyperthermia 21(2):169–183. doi:10.1080/02656730400003401
Hildebrandt B, Wust P, Ahlers O et al (2002) The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 43:33–56. doi:10.1016/S1040-8428(01)00179-2
Blaha M, Kohl J, Dubose D et al (2001) Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model. In Vitro Mol Toxicol 14:15–23. doi:10.1089/109793301316882513
Matylevitch NP, Schuschereba ST, Mata JR et al (1998) Apoptosis and accidental cell death in culture human keratinocytes after thermal injury. Am J Pathol 153:567–577
Schieke SM, Schroeder P, Krutmann J (2003) Cutaneous effects of infrared radiation: from clinical observations to molecular response mechanisms. Photodermatol Photoimmunol Photomed 19:228–234. doi:10.1034/j.1600-0781.2003.00054.x
Tamada Y, Takama H, Kitamura T et al (1994) Identification of programmed cell death in normal human skin tissues by using specific labeling of fragmented DNA. Br J Dermatol 131:521–524
Boehm I (2006) Apoptosis in physiological and pathological skin: implications for therapy. Curr Mol Med 6:375–394. doi:10.2174/156652406777435390
Kulms D, Zeise E, Poppelmann B et al (2002) DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogen 21:5844–5851. doi:10.1038/sj.onc.1205743
Leverkus M, Yaar M, Gilchrist BA (1997) Fas/Fas ligand interaction contribute to UV-induced apoptosis in human keratinocytes. Exp Cell Res 232:255–262. doi:10.1006/excr.1997.3514
Salah-Eldin AE, Inoue S, Tsukamoto S et al (2003) An association of Bcl-2 phosphorylation and Bax localization with their functions after hyperthermia and paclitaxel treatment. Int J Cancer 103:53–60. doi:10.1002/ijc.10782
Moody CA, Fradet-Turcotte A, Archambault J et al (2007) Human papillomaviruses activate caspases upon epithelial differentiation to induce viral genome amplification. Proc Natl Acad Sci USA 104:19541–19546. doi:10.1073/pnas.0707947104
Tollefson AE, Hermiston TW, Lichtenstein DL et al (1998) Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Nature 392:726–730. doi:10.1038/33712
Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89. doi:10.1038/32183
Acknowledgments
This study was supported by National Science Foundation (30740082), Program for New Century Excellent Talents in University (NCEP-04-0287) and Program for Changjiang Scholars and Innovative Research Team in University (IRT0760), Ministry of Education.
The authors declare that they have no conflict of interest.
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Wang, X., Gao, XH., Li, X. et al. Local hyperthermia induces apoptosis of keratinocytes in both normal skin and condyloma acuminata via different pathways. Apoptosis 14, 721–728 (2009). https://doi.org/10.1007/s10495-009-0344-8
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DOI: https://doi.org/10.1007/s10495-009-0344-8