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- Title
Tumor necrosis factor-α stimulates fractalkine production by mesangial cells and regulates monocyte transmigration: Down-regulation by cAMP.
- Authors
Chen, Yung-Ming; Lin, Shuei-Liong; Chen, Ching-Wen; Chiang, Wen-Chih; Tsai, Tun-Jun; Hsieh, Bor-Shen
- Abstract
Tumor necrosis factor-α stimulates fractalkine production by mesangial cells and regulates monocyte transmigration: Down-regulation by cAMP. Background. Fractalkine is a CX3 C chemokine for mononuclear cells that has been implicated in the recruitment and accumulation of monocytes seen in glomerular diseases. We investigated the mechanisms by which tumor necrosis factor (TNF)-α stimulates mesangial cell (MC) fractalkine expression, and the effects of MC-derived fractalkine on monocyte transmigration. Methods. Cultured rat MCs were incubated with TNF-α, with or without pretreatment with pharmacologic inhibitors of protein kinases or transcriptional factors downstream to TNF-α. Fractalkine mRNA and protein were analyzed by Northern and Western blotting. Translocation of nuclear factor (NF)-κB was evaluated by immunocytochemical staining. Monocyte transmigration was determined by in vitro chemotaxis assay. Results. TNF-α stimulated MC fractalkine mRNA as well as cell-bound and soluble protein expression in a dose- and time-dependent manner. The soluble fractalkine was shed from the cell-bound form via metalloproteinase-dependent cleavage, and mediated in part TNF-α–induced monocyte transmigration in vitro. The incubation of MCs with calphostin C [a selective inhibitor of protein kinase C (PKC)] or PD98059 [a selective inhibitor of p42/44 mitogen-activated protein kinase (MAPK) kinase] attenuated TNF-α–stimulated fractalkine mRNA and protein expression. Coincubation of MCs with calphostin C and PD98059 resulted in a synergistic inhibition of TNF-α–stimulated fractalkine mRNA and protein expression. Incubation of MCs with phorbol myristate acetate (PMA) for four hours resulted in an increase in fractalkine mRNA expression that could be suppressed by calphostin C or depletion of PKC by pretreatment with PMA for 24 hours. Further, activation of PKC-depleted MCs with TNF-α stimulated...
- Subjects
CHEMOKINES; MONOCYTES
- Publication
Kidney International, 2003, Vol 63, Issue 2, p474
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00766.x