Endothelin-1 peptides and IL-5 synergistically increase the expression of IL-13 in eosinophils.
The 21-amino acid-length endothelin-1 (ET-1)(1-21) and its novel derivative, 31 amino acid-length ET-1(1-31), have proinflammatory properties and induce significant eosinophil migration mediated by an increase in the local levels of eotaxin and IL-5. We have analyzed by reverse transcription polymerase chain reaction and enzyme immunoassay the effects of ETs on the expression of IL-13 mRNA and protein in eosinophils with or without cell priming with IL-5. The expression of the ETA receptor (ETAR) and its membrane localization were detected in the eosinophils, whereas the ETB receptor was undetectable. ET peptides synergistically increased the expression of IL-13 in eosinophils after priming with IL-5, and the increase was blocked by the ETAR antagonist BQ123, though these peptides did not directly influence the expression. These results may explain the presence of eosinophilia in the airways' epithelium of patients suffering from asthma, along with an increase in immunoreactive ETs.
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
Ping
P
Cui
Saimoon
S
Sharmin
Yuushi
Y
Okumura
Hiroshi
H
Yamada
Mihiro
M
Yano
Dai
D
Mizuno
Hiroshi
H
Kido
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D018793:Interleukin-13 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044022:Receptor, Endothelin A / Q000096:biosynthesis; D044023:Receptor, Endothelin B / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D015854:Up-Regulation
C515351:Ccr3 protein, mouse; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D018793:Interleukin-13; D015848:Interleukin-5; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)