Mechanical stretch and angiotensin II increase interleukin-13 production and interleukin-13 receptor alpha2 expression in rat neonatal cardiomyocytes.
BACKGROUND
The high affinity receptor for interleukin (IL)-13, IL-13 receptor alpha2 (IL-13Ralpha2), acts as a decoy receptor for IL-13, modulates fibrosis and has an anti-tumor effect. Recently, IL-13Ralpha2 has been considered as a therapeutic target for fibrosis and tumor growth. However, the mechanism of IL-13Ralpha2 expression in cardiomyocytes is unclear.


RESULTS
The mechanism of IL-13Ralpha2 expression was examined using cultured rat neonatal cardiomyocytes. Cyclical mechanical stretch induced IL-13Ralpha2 mRNA expression in rat cardiomyocytes. Treatment with angiotensin II, which plays a pivotal role in mechanical stretch-induced cardiomyocyte hypertrophy, upregulated IL-13Ralpha2 mRNA expression in rat cardiomyocytes. IL-13Ralpha2 mRNA expression was also upregulated through IL-13 treatment. Furthermore, mechanical stretch and angiotensin II treatment caused IL-13 secretion from rat cardiomyocytes, which was suppressed by angiotensin type1 receptor (AT1R) RNA interference. Upregulation of IL-13Ralpha2 mRNA expression through mechanical stretch, angiotensin II treatment and IL-13 treatment was inhibited by anti-IL-13Ralpha1 antibody and STAT6 depletion through RNA interference. Positive immunohistochemical staining for IL-13Ralpha2 was observed in the myocardium of endomyocardial biopsy specimens from the failing human heart, but not in autopsy specimens from control subjects.


CONCLUSIONS
IL-13 might act in an autocrine and paracrine fashion to upregulate IL-13Ralpha2 expression in cardiomyocytes.
Nishimura
Yuki
Y
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
Inoue
Teruo
T
Morooka
Toshifumi
T
Node
Koichi
K
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000187:drug effects
D017931:DNA Primers; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000804:Angiotensin II