Allergy Asthma Immunol Res.  2015 Mar;7(2):106-117. 10.4168/aair.2015.7.2.106.

Endoplasmic Reticulum Stress and the Related Signaling Networks in Severe Asthma

• Kim SR
• Lee YC

• KMID: 2365538
• DOI: http://doi.org/10.4168/aair.2015.7.2.106

Abstract

The endoplasmic reticulum (ER) is a specialized organelle that plays a central role in biosynthesis, correct protein folding, and posttranslational modifications of secretory and membrane proteins. Loss of homeostasis in ER functions triggers the ER stress response, resulting in activation of unfolded protein response (UPR), a hallmark of many inflammatory diseases. These pathways have been reported as critical players in the pathogenesis of various pulmonary disorders, including pulmonary fibrosis, lung injury, and chronic airway disorders. More interestingly, ER stress and the related signaling networks are emerging as important modulators of inflammatory and immune responses in the development of allergen-induced bronchial asthma, especially severe asthma.

Keyword

Severe asthma; steroid resistance; ER stress; UPR pathways

MeSH Terms

Asthma*
Endoplasmic Reticulum
Endoplasmic Reticulum Stress*
Homeostasis
Lung Injury
Membrane Proteins
Organelles
Protein Folding
Protein Processing, Post-Translational
Pulmonary Fibrosis
Unfolded Protein Response
Membrane Proteins

Figure

• 

  Figure The role of ER stress/UPR pathways and the integrated signaling networks in steroid-resistant inflammatory responses. Various allergens and pathogens evoke the activation of intracellular signaling networks, oxidative stress, and ER stress; they are also interlacing complicatedly. Among these components associated with ER stress and UPR branches, there are several molecular mechanisms for steroid resistance, for example, PI3K-δ, NF-κB, MAPK pathways, IL-17 production, and so on. The overlap molecular mechanisms between ER stress and steroid resistance provide insights into the key to resolve the obstacle for the management of severe asthma.

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