Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.
Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.
Nabata
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Fukuo
K
K
Morimoto
S
S
Kitano
S
S
Momose
N
N
Hirotani
A
A
Nakahashi
T
T
Nishibe
A
A
Hata
S
S
Niinobu
T
T
Suhara
T
T
Shimizu
M
M
Ohkuma
H
H
Sakurai
S
S
Nishimaki
H
H
Ogihara
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004347:Drug Interactions; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D006025:Glycosaminoglycans; D007376:Interleukin-2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011464:Epoprostenol; D002118:Calcium