Serum of patients with oral pemphigus vulgaris impairs keratinocyte wound repair in vitro: a time-lapse study on the efficacy of methylprednisolone and pyridostigmine bromide

  1. A Lanza1,2,†,
  2. A Stellavato3,†,
  3. I Heulfe4,
  4. C Landi2,
  5. F Gombos1,2,
  6. N Cirillo1,2,5

Article first published online: 10 JUN 2009

DOI: 10.1111/j.1601-0825.2009.01574.x

Issue

Oral Diseases

Oral Diseases

Volume 15, Issue 7, pages 478–483, October 2009

Additional Information

How to Cite

Lanza, A., Stellavato, A., Heulfe, I., Landi, C., Gombos, F. and Cirillo, N. (2009), Serum of patients with oral pemphigus vulgaris impairs keratinocyte wound repair in vitro: a time-lapse study on the efficacy of methylprednisolone and pyridostigmine bromide. Oral Diseases, 15: 478–483. doi: 10.1111/j.1601-0825.2009.01574.x

Author Information

  1. 1

    Regional Center on Craniofacial Malformations-MRI, II University of Naples, Naples, Italy

  2. 2

    AISS Accademia Italiana di Stomatologia Sperimentale, Naples, Italy

  3. 3

    Department of Experimental Medicine, 1st School of Medicine and Surgery, II University of Naples, Naples, Italy

  4. 4

    Bristol Dental Hospital, Bristol, UK

  5. 5

    Department of Oral and Dental Science, University of Bristol, Bristol, UK

  1. †

    These authors contributed equally to this study.

*Dr N Cirillo, Department of Oral Sciences, Second University of Naples, Via Luigi de Crecchio, 6, 80138 Naples, Italy. Tel: +39 081 5665507, Fax: +39 0815665500, E-mail: cirillo.sun@libero.it

Publication History

  1. Issue published online: 10 SEP 2009
  2. Article first published online: 10 JUN 2009
  3. Received 8 August 2008; revised 19 April 2009; accepted 23 April 2009

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Keywords:

  • pemphigus vulgaris;
  • keratinocytes;
  • corticosteroids;
  • cholinergic agonists;
  • wound healing

Objectives:  Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting primarily oral mucosa and skin. Among the drugs used for the therapy of pemphigus, both methylprednisolone (MP) and pyridostigmine bromide (PBr) can prevent acantholysis in vitro. However, their putative therapeutic properties in regenerating PV-like lesions and promoting the healing process still remain to be demonstrated. To address this issue, here we have developed a model for studying the process of epithelial cleft regeneration in PV by artificially wounding keratinocyte monolayers.

Materials and methods:  The experimental model was established by scratching confluent monolayers to simulate the epithelial cleft; then, wound regeneration in the presence of submaximal concentrations of PV sera was studied by time-lapse microscopy, with or without the addition of MP and PBr in the culture medium.

Results:  Pemphigus vulgaris serum inhibited epithelial cleft repair of wounded monolayers. Indeed, in the presence of 10% (v/v) PV serum, keratinocytes reached only 2% confluence within 72 h vs an almost complete healing of controls. When administered together with PV sera, MP significantly (P < 0.01) enhanced wound fill by 30% after 72 h. PV-associated wound repair was significantly (P < 0.05) ameliorated by PBr by 24 h and keratinocytes reached 20% confluence after 72 h. Interestingly, neither MP nor PBr could accelerate wound healing when compared with untreated control monolayers.

Conclusions:  In PV, MP and PBr exert their curative effects in part by enhancing the regeneration properties of keratinocytes. Indeed, our data suggest that both drugs can specifically counterbalance the detrimental effects of PV serum on keratinocyte wound healing. These findings provide an explanation for the efficacy of MP and PBr in the treatment of PV lesions in human skin and oral mucosa.

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