Original Paper

Neurochemical Research

, Volume 35, Issue 6, pp 899-908

First online:

Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ c null and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

  • L. DanielyanAffiliated withDepartment of Clinical Pharmacology, University Hospital of Tuebingen
  • , S. VerleysdonkAffiliated withInterfaculty Institute for Biochemistry, University of Tuebingen
  • , M. BuadzeAffiliated withDepartment of Clinical Pharmacology, University Hospital of Tuebingen
  • , C. H. GleiterAffiliated withDepartment of Clinical Pharmacology, University Hospital of Tuebingen
  • , G. H. BuniatianAffiliated withH. Buniatian Institute of Biochemistry Email author 

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Abstract

Most skin pathologies are characterized by unbalanced synthesis of major histocompatability complex II (MHC-II) proteins. Healthy skin keratinocytes simultaneously produce large amounts of MHC-II and regeneration-supporting proteins, e.g. erythropoietin (EPO), EPO receptor (EPOR), glutamine synthetase (GS) and metallothionein (MT). To investigate the level of regeneration-supporting proteins in the skin during misbalanced production of MHC-II, skin sections from nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γ c null and or Foxn1 nu/nu mice which are a priory known to under- and over-express MHC II, respectively, were used. Double immunofluorescence analysis of NOD/SCID/γ c null skin sections showed striking decrease in expression of MHC-II, EPO, GS and MT. In Foxn1 nu/nu mouse skin, GS was strongly expressed in epidermis and in hair follicles (HF), which lacked EPO. In nude mouse skin EPO and MHC-II were over-expressed in dermal fibroblasts and they were completely absent from cortex, channel, medulla and keratinocytes surrounding the HF, suggest a role for EPO in health and pathology of hair follicle. The level of expression of EPO and GS in both mutant mice was confirmed by results of Western blot analyses. Strong immunoresponsiveness of EPOR in the hair channels of NOD/SCID/γ c null mouse skin suggests increased requirements of skin cells for EPO and possible benefits of exogenous EPO application during disorders of immune system accompanied by loss MHC-II in skin cells.

Keywords

Blood-tissue barrier EPO receptor Glial fibrillary acidic protein Immunodeficiency Keratinocytes Nudity