Seminars in Immunopathology

, Volume 35, Issue 3, pp 293–306 | Cite as

The UPR and lung disease

Review
First Online:
Received:
Accepted:

Abstract

The respiratory tract has a surface area of approximately 70 m2 that is in direct contact with the external environment. Approximately 12,000 l of air are inhaled daily, exposing the airway epithelium to up to 25 million particles an hour. Several inhaled environmental triggers, like cigarette smoke, diesel exhaust, or allergens, are known inducers of endoplasmatic reticulum (ER) stress and cause a dysregulation in ER homeostasis. Furthermore, some epithelial cell types along the respiratory tract have a secretory function, producing large amounts of mucus or pulmonary surfactant, as well as innate host defense molecules like defensins. To keep up with their secretory demands, these cells must rely on the appropriate functioning and folding capacity of the ER, and they are particularly more vulnerable to conditions of unresolved ER stress. In the lung interstitium, triggering of ER stress pathways has a major impact on the functioning of vascular smooth muscle cells and fibroblasts, causing aberrant dedifferentiation and proliferation. Given the large amounts of foreign material inhaled, the lung is densely populated by various types of immune cells specialized in engulfing and killing pathogens and in secreting cytokines/chemokines for efficient microbial clearance. Unfolded protein response signaling cascades have been shown to intersect with the functioning of immune cells at all levels. The current review aims to highlight the role of ER stress in health and disease in the lung, focusing on its impact on different structural and inflammatory cell types.

Keywords

Endoplasmatic Reticulum Stress Pulmonary Arterial Hypertension Idiopathic Pulmonary Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Airway Epithelium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AEC

Alveolar epithelial cell

AGR2

Anterior gradient homolog 2

ATF6

Activating transcription factor 6

CHOP

CCAAT/enhancer-binding protein homologous protein

CF

Cystic fibrosis

CFTR

Cystic fibrosis transmembrane conductance regulator

ChIP

Chromatin immunoprecipitation

CREB

cAMP response element binding

COPD

Chronic obstructive pulmonary disease

CRT

Calreticulin

CS

Cigarette smoke

DCs

Dendritic cells

ECs

Epithelial cells

eIF2a

Elongation initiation factor 2α

ER

Endoplasmatic reticulum

ERAD

ER-associated degradation

Foxo2a

Forkhead box-family transcription factor 2a

GASML

Gasdermin B

GCM

Goblet cell metaplasia

GCN2

General control nonrepressed

Grp78

Glucose regulated protein 78

HDM

House dust mite

IPF

Idiopathic pulmonary fibrosis

IIPs

Idiopathic interstitial pneumonias

IRE1

Inositol requiring enzyme 1

JNK

c-Jun N-terminal kinase

NO

Nitric oxide

Nrf-2

Nuclear factor erythroid 2-related factor

ORMDL3

Orosomucoid-like 3

PAH

Pulmonary arterial hypertension

PDI

Protein disulfide isomerase

PERK

Protein kinase R-like ER kinase

PM

Particulate matter

RIDD

Regulated IRE1-dependent decay

ROS

Reactive oxygen species

S1P

Sphingosine-1 phosphate

SERCA

Sarco-endoplasmic reticulum Ca2+ ATPase pump

SMC

Smooth muscle cells

SPDEF

SAM pointed domain containing Ets

SPC

Surfactant protein C

TGF-β

Transforming growth factor β

TLR4

Toll-like receptor 4

UPR

Unfolded protein response

XBP1

X-box binding protein 1

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Fabiola Osorio
    • 1
    • 2
  • Bart Lambrecht
    • 1
    • 2
  • Sophie Janssens
    • 1
    • 2
  1. 1.GROUP-ID Consortium, Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory DiseasesUniversity HospitalGhentBelgium
  2. 2.Department of Molecular Biomedical ResearchVIBGhentBelgium

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