IL-10 inhibits the adhesion of leukocytic cells to IL-1-activated human endothelial cells

doi:10.1016/0165-2478(94)00226-H

Immunology Letters

Volume 45, Issues 1–2, February 1995, Pages 61-65

https://doi.org/10.1016/0165-2478(94)00226-H Get rights and content

Abstract

Cytokines play an important role in the recruitment of leukocytes from blood to sites of tissue injury and inflammation. Previous studies showed that the pro-inflammatory cytokine, IL-1, induces the adhesion of leukocytes by up-regulating the expression of the adhesion molecules ICAM-1 and VCAM-1 on endothelial cells. IL-10, a pleiotropic mediator, inhibits the production of cytokines by macrophages and down-regulates the antigen-presenting function of macrophages, thereby acting as a suppressor of immune responses. This study was undertaken to evaluate the effect of IL-10 on the adhesion of leukocytic cells to human umbilical vein endothelial cells. IL-10 inhibited the adhesion of a human monocytic cell line (THP-1) and a human lymphoblastic T-cell line (MOLT-4) to IL-1-stimulated endothelial cells. IL-10 also down-regulated the expression of ICAM-1 and VCAM-1 on IL-1-activated endothelial cells. IL-10-treated THP-1 cells adhered less than untreated THP-1 cells to IL-1-activated endothelial cells, whereas direct treatment of MOLT-4 had minimal effect on its adhesion to cytokine-activated endothelial cells. These results suggest that IL-10 counteracts the pro-inflammatory effects of IL-1 and regulates the adhesion of leukocytic cells to endothelial cells.

References (14)

T.M. Carlos et al.
Blood
(1990)
M.P. Bevilacqua
Annu. Rev. Immunol.
(1993)
T.M. Carlos et al.
Immunol. Rev.
(1990)
T.A. Springer
Nature
(1990)
D.F. Florentino et al.
J. Exp. Med.
(1989)
C. Bogdan et al.
J. Exp. Med.
(1991)
T. Krakauer
J. Immunol. Meth.
(1994)

There are more references available in the full text version of this article.

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These data suggested that intratracheal administered IL-10 down-regulated the expressions of ICAM-1 and VCAM-1 on pulmonary vascular endothelial cells via binding to IL-10R1, leading to the inhibition of eosinophilic and neutrophilic infiltrations. Indeed, Krakauer demonstrated that IL-10 downregulated the expressions of VCAM-1 and ICAM-1 on IL-1-activated human endothelial cells, followed by inhibiting the adhesion of leukocytes [43]. Other groups also reported that IL-10 significantly decreased VCAM-1 [44] and ICAM-1 [45] protein levels in mouse cerebrovascular endothelial cells and human coronary artery endothelial cells, respectively.
Subgroups of patients with severe asthma showing marked increases in sputum eosinophils and/or neutrophils are insensitive to corticosteroids. Previous reports have shown that exogenous administration of an anti-inflammatory cytokine, interleukin (IL)-10 negatively regulated both eosinophilic and neutrophilic migration into tissues. The objective of this study was to elucidate whether intratracheal IL-10 administration suppresses asthmatic responses in a steroid-insensitive model of mice. Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 500 µg/animal four times. Dexamethasone (1 mg/kg, intraperitoneal) or IL-10 (25 ng/mouse, intratracheal) was administered during the multiple challenges. The number of leukocytes, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-10 receptor in the lung, and the development of airway remodeling and hyperresponsiveness were evaluated after the fourth challenge. Consistent with our previous study, dexamethasone hardly suppressed the development of airway remodeling and hyperresponsiveness. Although intratracheal IL-10 administration did not affect the development of airway remodeling, the infiltration of eosinophils and neutrophils, and the development of airway hyperresponsiveness were significantly inhibited. Moreover, IL-10 administration significantly decreased the numbers of ICAM-1⁺ and VCAM-1⁺ pulmonary vascular endothelial cells, which express IL-10 receptor 1, even though neither production of eosinophilic nor neutrophilic cytokines in the lung was inhibited. Therefore, IL-10 can suppress eosinophil and neutrophil infiltration by inhibiting the proliferation of ICAM-1⁺ and VCAM-1⁺ pulmonary vascular endothelial cells, resulting in inhibition of airway hyperresponsiveness in steroid-insensitive asthmatic mice. IL-10 replacement therapy may be clinically useful for the treatment of steroid-insensitive asthma.
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Atherosclerosis is a chronic inflammatory disease that results in the formation of lipid-laden plaques within vascular walls. Although treatments using drugs and antibodies are now beginning to address the inflammation in atherosclerosis, neither is sufficient for long-term therapy. In this paper, we introduce a strategy to deliver genes encoding the anti-inflammatory protein interleukin-10 (IL-10) in vivo. We showed that Branched Poly(ß-aminoester) carrying the IL-10 gene are able to localize specifically at the plaque via surface-functionalized targeting moieties against inflamed VCAM-1 and/or ICAM-1 and to facilitate gene transcription by ECs to increase the local concentration of the IL-10 within the plaque. To date, there is no report involving non-viral nanotechnology to provide gene-based therapies for atherosclerosis.
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Patients with end-stage renal failure depend on hemodialysis indefinitely without renal transplantation, requiring a long-term patent vascular access. Although an arteriovenous fistula (AVF) remains the preferred vascular access for hemodialysis because of its longer patency and fewer complications compared with other vascular accesses, the primary patency of AVF is only 50% to 60%, presenting a clinical need for improvement. AVF mature by developing a thickened vascular wall and increased diameter to adapt to arterial blood pressure and flow volume. Inflammation plays a critical role during vascular remodeling and fistula maturation; increased shear stress triggers infiltration of T cells and macrophages that initiate inflammation, with involvement of several different subsets of T cells and macrophages. We review the literature describing distinct roles of the various subsets of T cells and macrophages during vascular remodeling. Immunosuppression with sirolimus or prednisolone decreases neointimal hyperplasia during AVF maturation, suggesting novel approaches to enhance vascular remodeling. However, M2 macrophages and CD4⁺ T cells play essential roles during AVF maturation, suggesting that total immunosuppression may suppress adaptive vascular remodeling. Therefore, it is likely that regulation of inflammation during fistula maturation will require a balanced approach to coordinate the various inflammatory cell subsets. Advances in immunosuppressive drug development and delivery systems may allow for more targeted regulation of inflammation to improve vascular remodeling and enhance AVF maturation. (JVS–Vascular Science 2020;1:207-18.)
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Both cellular and viral IL-10 have been shown to inhibit the production of chemokines, such as CCL2, CCL3, and CCL5 (Imlach et al., 2002; Wise et al., 2007, 2014), which are key chemoattractants for monocytes, mast cells and DC (Sabatté et al., 2007; Shi and Pamer, 2011; Halova et al., 2012). Also the IL-10s suppress production of cytokines such as TNF and IL-1β (Imlach et al., 2002; Wise et al., 2007, 2014), which stimulate endothelial cell expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and the extravasation of immune cells (Krakauer, 1995; Kawachi et al., 2000). Moreover, cellular IL-10 can down regulate the expression of adhesion molecules on immune cells including l-selectin and β2-integrin (Inoue, 2000; Mtairag et al., 2001).
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IL-10 inhibits the adhesion of leukocytic cells to IL-1-activated human endothelial cells

Abstract

Blood

Annu. Rev. Immunol.

Immunol. Rev.

Nature

J. Exp. Med.

J. Exp. Med.

J. Immunol. Meth.