Regulation of endothelial and mesothelial cell function by interleukin-13: selective induction of vascular cell adhesion molecule-1 and amplification of interleukin-6 production.
The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular endothelial cells (EC). In vitro exposure to IL-13 of human umbilical vein EC induced surface expression of vascular cell adhesion molecule-1 (VCAM-1). At optimal concentrations (10 to 50 ng/mL) and exposure times (24 hours), IL-13 was a twofold to threefold less effective inducer of VCAM-1 than IL-1, which was used as reference EC activator. When IL-13 was combined with IL-1, an almost additive induction of VCAM-1 was observed. Induction of VCAM-1 by IL-13 was selective in that E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unaffected. IL-13 caused a modest reduction of IL-1 induction of E-selectin and ICAM-1. Surface expression of VCAM-1 on IL-13-treated cells was associated with mRNA induction (as assessed by Northern analysis and reverse transcriptase-polymerase chain reaction), with predominance of transcripts encoding the 7 Ig domain form of this molecule. In agreement with previous reports, IL-13 inhibited cytokine production in human monocytes. In contrast, IL-13 was a weak inducer and an amplifier (in concert with IL-1) of IL-6 expression in EC. Mesothelial cells, which share properties with EC and regulate the traffic and function of leukocytes in serosal cavities, were stimulated to express VCAM-1 and IL-6 by IL-13. Thus, IL-13 elicits a spectrum of responses in vascular endothelium remarkably similar to that of IL-4 and IL-10. Interaction of these cytokines with vascular endothelium may play an important role in the induction and expression of Th2-dependent responses.
Sironi
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Sciacca
F L
FL
Matteucci
C
C
Conni
M
M
Vecchi
A
A
Bernasconi
S
S
Minty
A
A
Caput
D
D
Ferrara
P
P
Colotta
F
F
D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology*; D008648:Mesoderm / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase; D011994:Recombinant Proteins / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D018793:Interleukin-13; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D012194:RNA-Directed DNA Polymerase