IL-33 precursor and bleomycin synergize in inducing lymphocyte accumulation and fibrosis in the lungs
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1
University of Maryland School of Medicine, United States
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2
Baltimore VA Medical Center, United States
We and others have previously found that precursor IL-33 (PRIL33) protein is biologically active without proteolytic activation. We reported that the levels of PRIL33 are substantially elevated in the lungs of patients with interstitial lung disease (ILD), which is associated with idiopathic pulmonary fibrosis and systemic sclerosis. PRIL33 remains intranuclear and promotes inflammation in a non-Th2 fashion by not engaging the mature IL-33 receptor T1/ST2. To further assess the biological role of the elevated expression of PRIL33 in ILD, intratracheal bleomycin injury to the lung, alone or in combination with recombinant adenovirus delivery of PRIL33, was used to model ILD in mice. Combined PRIL33 gene delivery and bleomycin challenge had a potentiating effect on pulmonary lymphocytosis; accumulation of collagen; expression of HSP70; and the levels of TGF-β, CCL6, MCP-1, and MIP-1α, with these combined effects significantly exceeding the sum of the effects of PRIL33 gene delivery or bleomycin challenge alone (p < 0.05). By contrast, the combined effects of PRIL33 expression and bleomycin on bronchoalveolar lavage counts of macrophages and neutrophils in these mice were additive of the effects of each of these factors alone. The Th2 cytokines IL-4, IL-5, and IL-13 were not part of this synergy, and gene deficiency of T1/ST2 did not affect the synergistic nature of the “double-hit” from PRIL33 expression and bleomycin injury. It was concluded that elevated PRIL33 expression in ILD is a likely contributor to inflammatory and fibrotic lung injury, and that this contribution is independent of the T1/ST2 receptor or Th2 cytokines.
Keywords:
interleukin-33,
Inflammation,
Fibrosis,
Lung,
Scleroderma, Systemic,
Idiopathic Pulmonary Fibrosis
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Luzina
IG,
Lockatell
V,
Kopach
P,
Todd
NW and
Atamas
SP
(2013). IL-33 precursor and bleomycin synergize in inducing lymphocyte accumulation and fibrosis in the lungs.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00859
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Received:
18 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Sergei P Atamas, University of Maryland School of Medicine, Baltimore, Maryland, United States, satamas@som.umaryland.edu