title: Rat mesangial cells exhibit sex-specific profibrotic and proinflammatory phenotypes.
abstract: BACKGROUND
  Chronic renal disease progresses more rapidly in males compared to females. This study investigated whether there were any inherent differences between male and female mesangial cells that could contribute to this phenomenon and whether these differences could be modulated by sex hormones.
  
  
  METHODS
  Experiments were carried out on cultured mesangial cells derived from adult male and female Wistar rat kidneys. Fibronectin, TNFalpha and IL-1beta levels were measured in control and macrophage-conditioned medium (MCM)-injured cells in the presence and absence of 17beta estradiol or testosterone.
  
  
  RESULTS
  Male mesangial cells expressed higher baseline fibronectin levels compared to female cells. Similarly, basal levels of the proinflammatory cytokines TNFalpha and IL-1beta were higher in male cells. Fibronectin and IL-1beta levels were enhanced proportionately between the sexes in response to MCM stimulation, whilst the increase in TNFalpha levels was greater in MCM-stimulated female cells. Treatment with 10(-8) M estradiol down-regulated baseline fibronectin levels in female mesangial cells but had no effect on basal levels in male cells. Estradiol had no effect on MCM-stimulated fibronectin levels in female mesangial cells but further increased stimulated levels in male cells. Testosterone had no effect on basal fibronectin levels of either sex but further enhanced MCM-stimulated fibronectin levels in mesangial cells of both sexes. Sex hormone treatment had no effect on cytokine levels in male mesangial cells. However, in female cells estradiol decreased TNFalpha levels and increased IL-1beta levels, while testosterone increased the levels of both cytokines.
  
  
  CONCLUSIONS
  These data would suggest that male mesangial cells inherently exhibit greater profibrotic and proinflammatory characteristics than female cells. The inherent gender phenotypes are further modulated by sex hormones. This sexual dimorphism in mesangial cells may play a contributory role in the faster rate of progression to end-stage renal disease in males.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. izap1@le.ac.uk.
authors.forename: Izabella Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.forename: Eddie K C
authors.initials: EK
authors.lastname: Tan
authors.forename: Kevin P G
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005353:Fibronectins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D004958:Estradiol