title: Accumulation of C-reactive protein in basal keratinocytes of normal skins.
abstract: BACKGROUND
  C-reactive protein (CRP) is a prototypic acute phase protein which increases dramatically in the blood during the first 48h of tissue inflammation and has been recognized as a risk factor for atherosclerosis. CRP interacts with a variety of proteins.
  
  
  OBJECTIVE
  To know the role of accumulated CRP in the skin.
  
  
  METHODS
  Interaction of CRP with basal keratinocytes was studied using immunohistochemical method and keratinocyte culture system.
  
  
  RESULTS
  We found an immunohistochemical deposition of CRP on the basal keratinocyte membrane in some normal human skins (23 out of 46 skins). When added to cultured keratinocytes, heat-denatured but not native CRP was found to adhere to keratinocyte cell membrane after 1h, then internalized into cytoplasm after 24h. The heat-denatured CRP recognized at least four keratinocyte polypeptides with the molecular weights of 56, 42, 32 and 24kDa. Ligand binding assays suggested that multiple populations of receptor-ligand interactions were involved in the binding between CRP and keratinocyte. Cultured dermal microvascular endothelial cells were found to express CRP of which expression was greatly induced by interleukin-1β (IL-1β) treatment, suggesting that the deposited CRP in the basal keratinocytes can be derived from local dermal microvasculatures as well as from systemic circulation (serum). Treatment of cultured keratinocytes with heat-denatured CRP induced interleukin-8 (IL-8) expression, a potent leukocyte chemotactic cytokine. CRP in the medium (liquid phase) and CRP-coated dishes (solid phase) both inhibited the adhesion of keratinocytes in culture.
  
  
  CONCLUSIONS
  Accumulation of CRP may regulate the skin inflammation and keratinocyte proliferation by modulating keratinocyte cytokine expression and adhesion to substrate.
authors.affiliation: Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Electronic address: nfujimo@ndmc.ac.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Dermatology, Namiki Hospital, 5-2753 Higashi-Sayamagaoka, Tokorozawa, Saitama 359-1106, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Tajima
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D003872:Dermatitis / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000502:physiology; D055806:Microvessels / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D002097:C-Reactive Protein
keywords: C-reactive protein; Endothelial cell; IL-1β; IL-8; Keratinocyte