Alteration of Tight Junction Proteins Is an Early Event in Psoriasis : Putative Involvement of Proinflammatory Cytokines
AUTOR(ES)
Kirschner, Nina
FONTE
American Society for Investigative Pathology
RESUMO
Psoriasis is an inflammatory skin disease characterized by hyperproliferation of keratinocytes, impaired barrier function, and pronounced infiltration of inflammatory cells. Tight junctions (TJs) are cell-cell junctions that form paracellular barriers for solutes and inflammatory cells. Altered localization of TJ proteins in the epidermis was described in plaque-type psoriasis. Here we show that localization of TJ proteins is already altered in early-stage psoriasis. Occludin, ZO-1, and claudin-4 are found in more layers than in normal epidermis, and claudin-1 and -7 are down-regulated in the basal and in the uppermost layers. In plaque-type psoriasis, the staining patterns of occludin and ZO-1 do not change, whereas the claudins are further down-regulated. Near transmigrating granulocytes, all TJ proteins except for junctional adhesion molecule-A are down-regulated. Treatment of cultured keratinocytes with interleukin-1β and tumor necrosis factor-α, which are present at elevated levels in psoriatic skin, results in an increase of transepithelial resistance at early time points and a decrease at later time points. Injection of interleukin-1β into an ex vivo skin model leads to an up-regulation of occludin and ZO-1, resembling TJ protein alteration in early psoriasis. Our results show for the first time that alteration of TJ proteins is an early event in psoriasis and is not the consequence of the more profound changes found in plaque-type psoriasis. Our data indicate that cytokines are involved in alterations of TJ proteins observed in psoriasis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2731128Documentos Relacionados
- Regulation of Airway Tight Junctions by Proinflammatory Cytokines
- Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti‐citrulline autoreactivity is associated with up regulation of proinflammatory cytokines
- Slit Diaphragms Contain Tight Junction Proteins
- Tight Junction Proteins in Human Schwann Cell Autotypic Junctions
- Activation of Jun kinase is an early event in hepatic regeneration.