title: Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nabata
authors.forename: K
authors.initials: K
authors.lastname: Fukuo
authors.forename: S
authors.initials: S
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Kitano
authors.forename: N
authors.initials: N
authors.lastname: Momose
authors.forename: A
authors.initials: A
authors.lastname: Hirotani
authors.forename: T
authors.initials: T
authors.lastname: Nakahashi
authors.forename: A
authors.initials: A
authors.lastname: Nishibe
authors.forename: S
authors.initials: S
authors.lastname: Hata
authors.forename: T
authors.initials: T
authors.lastname: Niinobu
authors.forename: T
authors.initials: T
authors.lastname: Suhara
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Ohkuma
authors.forename: S
authors.initials: S
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Nishimaki
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: 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*
chemical_list: D006025:Glycosaminoglycans; D007376:Interleukin-2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011464:Epoprostenol; D002118:Calcium