Tomoregulin ectodomain shedding by proinflammatory cytokines.
The shedding mechanism for the tomoregulin (TR) ectodomain, which contains two follistatin modules and a single epidermal growth factor (EGF)-like domain, remains unclear. Our study provides the first evidence that proinflammatory cytokines, IL-1beta and TNF-alpha, induce TR-ectodomain shedding in cultured A172 human glioma cells, without affecting TR mRNA expression. In addition, it appears that this shedding process is induced via activation of the NF-kappaB signaling pathway; with consequent increase in the production of metalloproteinases. Furthermore, since due to erbB4 tyrosine phosphorylation TR may have functions similar to EGF/neuregulin (NRG) family growth factors, our results suggest that following inflammation-induced injury, increases in TR shedding may contribute to tissue growth and repair in the central nervous system.
Lin
Hong
H
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Wada
Ken
K
Yonezawa
Masaoki
M
Shinoki
Kei
K
Akamatsu
Tomonori
T
Tsukui
Taku
T
Sakamoto
Choitsu
C
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D004151:Dipeptides / Q000494:pharmacology; D005910:Glioma; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004151:Dipeptides; D006877:Hydroxamic Acids; D007375:Interleukin-1; D008565:Membrane Proteins; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C099410:TAPI-2; C423567:TMEFF2 protein, human; C486585:Tmeff1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases