Proinflammatory stimuli

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

Meeuwsen S, Persoon-Deen C, Bsibsi M, Ravid JM, Noort JM (2003) Cytokme, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli. Glia 43 243-253. 

In vitro, l,25(OH)2D3 potently inhibits upregulation of activation markers after stimulation with mitogens or proinflammatory stimuli (see above). Most patient-related data were therefore also generated from in vitro stimulated cells of patients that were previously treated with l,25(OH)2D3. However, even under those conditions, results were variable or contradicted evidence from experiments where cells were directly exposed to l,25(OH)2D3 in vitro. Thus, the proliferative capacity of Tcells from l,25(OH)2D3-treated hemodialysis patients to mitogens or conventional antigens was found unchanged [150,162]. IL-1 and IL-6 were transiently increased in one study after stimulation with PMA or LPS [163], but decreased according to others [154, 164]. 

Laurent TC, Fraser JR. Hyaluronan. FASEB J 1992 6 2397-2404. Mohamadzadeh M, DeGrendele H, Arizpe H, Estess P, Siegelman M. Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest 1998 101 97-108. Adamia S, Maxwell CA, Pilarski LM. Hyaluronan and hyaluronan synthases potential therapeutic targets in cancer. Curr Drug Targets Cardi-ovasc Haematol Disord 2005 5 3-14. 

Injection of mice with bacterial lipopolysaccharide OLPS) augmented the induction of disease by anti-MPO (61). This was accompanied by increased circulating tumor necrosis factor a (TNF-a), which has been shown in vitro to enhance activation of neutrophils by ANCA (40,41). Treatment with anti-TNF-a attenuated, but did not prevent, the LPS-mediated aggravation of anti-MPO IgG-induced glomerulonephritis. Thus, synergistic proinflammatory stimuli augment ANCA induced pathogenic events in vivo and in vitro. This corresponds to the... 

T.K. Baginski, K. Dabbagh, C. Satjawatcharaphong, D.C. Swinney, Cigarette smoke synergistically enhances respiratory mucin induction by proinflammatory stimuli. Am. J. Respir. Cell Mol. Biol. 32 (5) (2006) 165-174. 

Mohamadzadeh M, DeGrendele H, Arizpe H, Estess P, Siegelman M. Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest 1998 101 97-108. 

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