Glucocorticoid inhibition of interleukin-4 (IL-4) and interleukin-13 (IL-13) induced up-regulation of arginase in rat airway fibroblasts.
Arginase appears to play a significant role in the pathogenesis of inflammatory and obstructive airway diseases by interfering with NO synthesis (hyperreactivity) and by providing substrate for collagen synthesis (remodelling). IL-4 and IL-13 are key proinflammatory cytokines in asthma, and their effects on arginase in rat primary airway fibroblasts in culture were studied. Airway fibroblasts showed significant arginase activity, which was higher when the culture medium contained 10% fetal calf serum (FCS) (20 mU/mg protein) compared to 5% FCS (6 mU/mg protein). In presence of 10% FCS addition of IL-4 or IL-13 (10 ng/ml each) for 20 h or 40 h caused an increase in arginase activity by 76% and 160% (IL-4) and by 134% and 213% (IL-13), respectively. Using RT-PCR mRNA for arginase I was clearly detectable with 30 PCR cycles, whereas mRNA for arginase II was hardly detectable with 35 PCR cycles. IL-4 and IL-13 caused a clear increase in the mRNA of both arginase isoenzymes. Dexamethasone (1 microM) did not affect basal arginase activity, but largely opposed the stimulatory effects of IL-4 and IL-13. In conclusion, IL-4 and IL-13 can cause a marked up-regulation of arginase activity in rat airway fibroblasts and these effects can be inhibited by glucocorticoids.
Lindemann
Dirk
D
Institut für Pharmakologie und Toxikologie der Universität Bonn, Reuterstrasse 2b, 53113 Bonn, Germany.
Racké
Kurt
K
D000818:Animals; D001119:Arginase / Q000096:biosynthesis* / Q000235:genetics; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007527:Isoenzymes; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D044967:Serum / Q000502:physiology; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D003470:Culture Media; D005938:Glucocorticoids; D018793:Interleukin-13; D007527:Isoenzymes; D012333:RNA, Messenger; D015847:Interleukin-4; D003907:Dexamethasone; D001119:Arginase