title: Mechanism of steroid action in renal epithelial cells.
abstract: Renal tubular epithelial cells (TEC) are thought to play an active role in tubulointerstitial inflammation. Various immune and non-immune factors activate TEC to produce a variety of cytokines and chemokines, contributing to attraction of inflammatory cells to the kidney. The proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) appears to be a key player in these responses and tubular expression of NF-kappaB has been demonstrated in vitro and in vivo. Although glucocorticoids are known to inhibit NF-kappaB activation at different levels, the proinflammatory capacity of TEC was not inhibited. In contrast, glucocorticoids seemed to enhance the profibrotic response of TEC, emphasizing the cell-type specific characteristics of glucocorticoid action. We propose that specific inhibition of NF-kappaB activation in TEC might be an attractive strategy for therapeutic intervention in renal inflammation.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: de Haij
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009393:Nephritis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction; D013256:Steroids / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D016328:NF-kappa B; D013256:Steroids