Neurochemical Research

, Volume 35, Issue 6, pp 899–908

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

  • L. Danielyan
  • S. Verleysdonk
  • M. Buadze
  • C. H. Gleiter
  • G. H. Buniatian
Original Paper

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)/γcnull 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/γcnull 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/γcnull 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 

Abbreviations

CNS

Central nervous system

CLS

Confocal laser scanning

EPO

Erythopoietin

EPOR

Erythopoietin receptor

GFAP

Glial fibrillary acidic protein

GFAP-PC

Glial fibrillary acidic protein producing cells

GS

Glutamine synthetase

mAb

Monoclonal antibody

MHC II

Major histocompatibility class II complex

MT

Metallothionein

NOD/SCID/γcnull

Nonobese diabetic/severe combined immunodeficient nude/nude

OSHF

Outer sheet of hair follicle

pAb

Polyclonal antibody

PAGE

Polyacrylamide gel electrophoresis

PBS

Phosphate-buffered saline

SMAA

Smooth muscle alpha-actin

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • L. Danielyan
    • 1
  • S. Verleysdonk
    • 2
  • M. Buadze
    • 1
  • C. H. Gleiter
    • 1
  • G. H. Buniatian
    • 3
  1. 1.Department of Clinical PharmacologyUniversity Hospital of TuebingenTuebingenGermany
  2. 2.Interfaculty Institute for BiochemistryUniversity of TuebingenTuebingenGermany
  3. 3.H. Buniatian Institute of BiochemistryYerevanRepublic of Armenia

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