Next Article in Journal
Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture
Previous Article in Journal
Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States
Open AccessCommunication

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

1
Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
2
Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 2911; https://doi.org/10.3390/ijms19102911
Received: 4 September 2018 / Revised: 20 September 2018 / Accepted: 21 September 2018 / Published: 25 September 2018
(This article belongs to the Section Biochemistry)
Cytokine interleukin 33 (IL-33) is constitutively expressed by epithelial barrier cells, and promotes the development of humoral immune responses. Along with other proinflammatory mediators released by the epithelium of airways and lungs, it plays an important role in a number of respiratory pathologies. In particular, IL-33 significantly contributes to pathogenesis of allergy and asthma; genetic variations in the IL33 locus are associated with increased susceptibility to asthma. Large-scale genome-wide association studies have identified minor “G” allele of the single-nucleotide polymorphism rs928413, located in the IL33 promoter area, as a susceptible variant for early childhood and atopic asthma development. Here, we demonstrate that the rs928413(G) allele creates a binding site for the cAMP response element-binding protein 1 (CREB1) transcription factor. In a pulmonary epithelial cell line, activation of CREB1, presumably via the p38 mitogen-activated protein kinases (MAPK) cascade, activates the IL33 promoter containing the rs928413(G) allele specifically and in a CREB1-dependent manner. This mechanism may explain the negative effect of the rs928413 minor “G” allele on asthma development. View Full-Text
Keywords: asthma; lung epithelium; inflammation; p38 MAPK pathway asthma; lung epithelium; inflammation; p38 MAPK pathway
Show Figures

Graphical abstract

MDPI and ACS Style

Gorbacheva, A.M.; Korneev, K.V.; Kuprash, D.V.; Mitkin, N.A. The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells. Int. J. Mol. Sci. 2018, 19, 2911.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop