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The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.

ABSTRACT: To characterize the expression and function of interleukin (IL) 19, a recently described T-helper 2 anti-inflammatory IL, on endothelial cell (EC) pathophysiological features.The expression and effects of anti-inflammatory ILs on EC activation and development of angiogenesis are uncharacterized. We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal, human coronary endothelium and can be induced in cultured human ECs by serum and basic fibroblast growth factor. IL-19 is mitogenic and chemotactic, and it promotes EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cordlike structure formation of cultured ECs and enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in gelatinous protein (Matrigel) plugs in vivo.To our knowledge, these data are the first to report expression of the anti-inflammatory agent, IL-19, in ECs; and the first to indicate that IL-19 is mitogenic and chemotactic for ECs and can induce the angiogenic potential of ECs.

SUBMITTER: Jain S

PROVIDER: S-EPMC3005139 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.

Jain Surbhi S Gabunia Khatuna K Kelemen Sheri E SE Panetti Tracee S TS Autieri Michael V MV

Arteriosclerosis, thrombosis, and vascular biology 20101021 1

<h4>Objective</h4>To characterize the expression and function of interleukin (IL) 19, a recently described T-helper 2 anti-inflammatory IL, on endothelial cell (EC) pathophysiological features.<h4>Methods and results</h4>The expression and effects of anti-inflammatory ILs on EC activation and development of angiogenesis are uncharacterized. We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal, human coronary endothelium and can be induced in c ...[more]

PMID: 20966397

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Project description:We elucidated the anti-inflammatory mechanisms of IL-38 in allergic asthma. Human bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly (I:C)/LyoVec or infection-related cytokine TNF-? to induce expression of cytokines/chemokines/adhesion molecules. House dust mite (HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in vivo. IL-38 significantly inhibited induced proinflammatory IL-6, IL-1?, CCL5, and CXCL10 production, and antiviral interferon-? and intercellular adhesion molecule-1 expression in the coculture system. Mass cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1, STAT3, p38 MAPK, ERK1/2, and NF-?B pathways, and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene RGS13. Intraperitoneal injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid (BALF) and lung homogenates. Histological examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia, together with reduced Th2, Th17, and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs, spleen, and lymph nodes. IL-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice, together with significantly decreased CCR3+ eosinophil numbers in the BALF and lungs, and a reduced percentage of human CD4+CRTH2+ Th2 cells in the lungs and mediastinal lymph nodes. Together, our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic asthma.

Dataset Information

The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.

Publications

The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.

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