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Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via the epidermal platelet-activating factor receptor

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Abstract

Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects, which are mediated by the PAF receptor (PAF-R). Our previous studies have demonstrated that ultraviolet B radiation (UVB) is a potent stimulus for PAF production, and that the presence of the PAF-R on epithelial cells results in an augmentation of UVB-induced apoptosis. Inasmuch as PAF-R activation results in numerous signal transduction pathways, the present study was designed to characterize the signal transduction pathway responsible for PAF-R-mediated enhanced UVB-induced cytotoxicity. Using a model system of PAF-R-negative and -positive epithelioid KB cells, we demonstrate that inhibitors of p38 MAP kinase block the augmentation of UVB-mediated apoptosis seen in PAF-R-positive KB cells. In contrast, pharmacological and/or molecular inhibition of other pathways linked to PAF-R activation including ERK MAP kinase and NFκB do not affect PAF-R-mediated cytotoxicity. This study demonstrates the important role that p38 MAP kinase plays in PAF-R-mediated augmentation of UVB cytotoxicity.

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References

  1. Ahn KS, Hahn BS, Kwack K, Lee EB, Kim YS (2006) Platycodin D-induced apoptosis through nuclear factor-kappaB activation in immortalized keratinocytes Eur J Pharmacol 537:1–11

    Article  PubMed  CAS  Google Scholar 

  2. Barber L, Spandau D, Rathman S, Murphy R, Johnson C, Kelley S, Hurwitz S, Travers J (1998) Expression of the platelet-activating factor receptor results in enhanced ultraviolet B radiation-induced apoptosis in a human epidermal cell line J Biol Chem 273:18891–18897

    Article  PubMed  CAS  Google Scholar 

  3. Ishii S, Nagase T, Shimizu T (2002) Platelet-activating factor receptor. Prost Other Lipid Mediat 68:599–609

    Article  Google Scholar 

  4. Kripke ML, Anathaswamy H (2003) Carcinogenesis: ultraviolet radiation. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI (eds) Dermatology in general Medicine. McGraw-Hill, New York, pp 797–804

    Google Scholar 

  5. Li T, Southall MD, Yi Q, Pei Y, Lewis D, Al-Hassani M, Spandau D, Travers JB (2003) The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines. J Biol Chem 278:16614–16621

    Article  PubMed  CAS  Google Scholar 

  6. Marathe G, Johnson C, Billings SD, Southall MD, Pei Y, Spandau D, Murphy RC, Zimmerman GA, McIntyre TM, Travers JB (2005) Ultraviolet B radiation generates PAF-like phospholipid mediators underlying cutaneous damage J Biol Chem 280:35448–35455

    Article  PubMed  CAS  Google Scholar 

  7. Marques SA, Dy L, Southall MD, Yi Q, Smietana E, Kapur R, Marques M, Travers JB, Spandau D (2002) The platelet-activating factor receptor activates the ERK MAP kinase and induces proliferation of epidermal cells through an EGF Receptor-dependent pathway. J Pharmacol Exp Therapeut 300:1026–1035

    Article  CAS  Google Scholar 

  8. Papoutsaki M, Moretti F, Lanza M, Marinari B, Sartorelli V, Guerrini L, Chimenti S, Levrero M, Costanzo A (2005) A p38-dependent pathway regulates DeltaNp63 DNA binding to p53-dependent promoters in UV-induced apoptosis of keratinocytes. Oncogene 24(46):6970–6975

    Article  PubMed  CAS  Google Scholar 

  9. Pei Y, Barber LA, Murphy RC, Johnson CA, Kelley SW, Dy LC, Fertel RH, Nguyen TM, Williams DA, Travers JB (1998) Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. J Immunol 161: 1954–1961

    PubMed  CAS  Google Scholar 

  10. Southall M, Isenberg J, Nakshatri H, Yi Q, Pei Y, Spandau D, Travers J (2001) The platelet-activating factor receptor protects epidermal cells from tumor necrosis factor (TNF) α and TNF-related apoptosis inducing ligand-induced apoptosis through an NF-кB-dependent process. J Biol Chem 276: 45548–45554

    Article  PubMed  CAS  Google Scholar 

  11. Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM (2003) Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Crit Rev Lin Lab Sci 40(6):643–672

    Article  CAS  Google Scholar 

  12. Travers J, Huff J, Rola-Plaeszczynski M, Gelfand E, Morelli J, Murphy R (1995) Identification of functional platelet-activating factor receptors on human keratinocytes. J Invest Dermatol 105:816–823

    Article  PubMed  CAS  Google Scholar 

  13. Walterscheid JP, Ullrich SE, Ngheim DX (2002) Platelet-activating factor, a molecular sensor for cellular damage, activates systemic immune suppression. J Exp Med 195:171–179

    Article  PubMed  CAS  Google Scholar 

  14. Wolf P, Ngheim DX, Walterscheid JP, Byrne S, Matsumura Y, Matsumura Y, Bucana C, Ananthaswamy HN, Ullrich SE (2006) Platelet-activating factor (PAF) is crucial in psoralen + UVA (PUVA)-induced immune suppression, inflammation, and apoptosis. Am J Path 169(3):795–805

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Drs. Raymond L. Konger and Dan Spandau for their advice in writing this paper. This research was supported in part by grants from the Riley Memorial Association, and the National Institutes of Health grants HL62996 and U19 AI070448 and Veteran’s Administration Merit Award.

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Authors and Affiliations

  1. Department of Dermatology, H. B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children Rm 2659, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, IN, 46202, USA

    Megan Landis, Qiaofang Yi, Ann-Marie Hyatt, Angela R. Travers, Davina A. Lewis & Jeffrey B. Travers

  2. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Megan Landis, Qiaofang Yi, Ann-Marie Hyatt, Angela R. Travers & Jeffrey B. Travers

  3. Richard L. Roudebush V.A. Medical Center, Indiana University School of Medicine, Indianapolis, IN, USA

    Jeffrey B. Travers

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  1. Megan Landis
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  2. Qiaofang Yi
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  3. Ann-Marie Hyatt
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  4. Angela R. Travers
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  5. Davina A. Lewis
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  6. Jeffrey B. Travers
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Correspondence to Jeffrey B. Travers.

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Landis, M., Yi, Q., Hyatt, AM. et al. Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via the epidermal platelet-activating factor receptor. Arch Dermatol Res 299, 263–266 (2007). https://doi.org/10.1007/s00403-007-0753-x

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  • DOI: https://doi.org/10.1007/s00403-007-0753-x

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