Allergy and Airway: Asthma IV |

IL-33 Promotes Airway Remodeling in Asthma Through ST2/ERK1/2/MSK1 Signal Pathway FREE TO VIEW

Liang Dong, PhD
Author and Funding Information

Qilu Hospital of Shandong University, Jinan, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A36. doi:10.1016/j.chest.2016.02.038
Text Size: A A A
Published online


SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Interleukin-33 (IL-33) dysregulation plays a critical role in the pathogenesis of asthma airway inflammation and remodeling. However, the cellular and molecular mechanisms of IL-33 in asthma remodeling remain unclear.

METHODS: Expression of IL-33 and ST2 was examined in lung specimens from patients with asthma using immunohischemical analysis. Human lung fibroblasts were pretreated with anti-ST2 antibody, U0126 and H89 respectively and then treated with IL-33 recombination protein. Then western blot, cell immunofluorescence and real-time quantitative PCR were used to determine the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and mitogen- and stress-activated protein kinase 1 (MSK1) and the expression of alpha smooth muscle actin (α-SMA) and collagen I. In addition, the effect of soluble ST2 (sST2) was tested in a mouse asthma model to determine if IL-33 blocking influences airway remodeling of asthma.

RESULTS: We found that expression of IL-33 and ST2 was upregulated in airway samples from patients with asthma. Furthermore, we showed in vitro that IL-33 induced α-SMA and collagen I expression via ST2-ERK1/2-MSK1 signaling pathway in human lung fibroblast. Using a mouse asthma model, we demonstrated that IL-33 neutralization by administration of sST2 inhibited IL-33/ST2-ERKI/2-MSK1signaling pathway and airway remodeling in vivo.

CONCLUSIONS: In conclusion, these data indicate that IL-33, binding with its receptor ST2, can induce α-SMA and collagens I expression in human lung fibroblast through ERK1/2/MSK1 signaling pathway.

CLINICAL IMPLICATIONS: IL-33 blocking by sST2 overcomes ovalbumin (OVA)-induced airway remodeling in vivo and may serve as a new therapeutic option for asthma.

DISCLOSURE: The following authors have nothing to disclose: Liang Dong

No Product/Research Disclosure Information




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543