PMID- 34191076
OWN - NLM
STAT- MEDLINE
DCOM- 20220111
LR  - 20240124
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 95
IP  - 8
DP  - 2021 Aug
TI  - Precision cut lung slices: an ex vivo model for assessing the impact of 
      immunomodulatory therapeutics on lung immune responses.
PG  - 2871-2877
LID - 10.1007/s00204-021-03096-y [doi]
AB  - Chronic inflammatory diseases of the respiratory tract, such as chronic 
      obstructive pulmonary disease (COPD) and asthma, are severe lung diseases that 
      require effective treatments. In search for new medicines for these diseases, 
      there is an unmet need for predictive and translatable disease-relevant in 
      vitro/ex vivo models to determine the safety and efficacy of novel drug 
      candidates. Here, we report the use of precision cut lung slices (PCLS) as a 
      potential ex vivo platform to study compound effects in a physiologically 
      relevant environment. PCLS derived from an elastase-challenged mouse model 
      display key characteristics of increased inflammation ex vivo, which is 
      exacerbated further upon challenge with LPS, mimicking the immune insult of a 
      pathogen triggering disease exacerbation. Such LPS-induced inflammatory 
      conditions are significantly abrogated by immunomodulatory agents targeting 
      specific inflammatory signaling pathways in the absence of cytotoxic effects in 
      lung slices. Thus, an ex vivo model of PCLS with a simulated pathogenic insult 
      can replicate proposed in vivo pharmacological effects and thus could potentially 
      act as a valuable tool to investigate the underlying mechanisms associated with 
      lung safety, therapeutic efficacy and exacerbations with infection.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Liu, Guanghui
AU  - Liu G
AD  - Respiratory and Immunology Safety, Clinical Pharmacology and Safety Sciences, 
      R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Saren, Linnea
AU  - Saren L
AD  - Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, R&D, 
      AstraZeneca, Gothenburg, Sweden.
FAU - Douglasson, Helena
AU  - Douglasson H
AD  - Bioscience Cough and in Vivo, Early Respiratory and Immunology, 
      BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Zhou, Xiao-Hong
AU  - Zhou XH
AD  - Patient Safety, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Aberg, Per M
AU  - Aberg PM
AD  - Respiratory and Immunology Safety, Clinical Pharmacology and Safety Sciences, 
      R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Ollerstam, Anna
AU  - Ollerstam A
AD  - Respiratory and Immunology Safety, Clinical Pharmacology and Safety Sciences, 
      R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Betts, Catherine J
AU  - Betts CJ
AD  - Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, 
      R&D, AstraZeneca, Cambridge, UK. Catherine.Betts@astrazeneca.com.
FAU - Balogh Sivars, Kinga
AU  - Balogh Sivars K
AUID- ORCID: 0000-0003-1150-2455
AD  - Clinical Testing, Global Procurement, Operations, AstraZeneca, Gothenburg, 
      Sweden. Kinga.Balogh-Sivars@astrazeneca.com.
LA  - eng
PT  - Journal Article
DEP - 20210630
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Immunomodulating Agents)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Immunity/drug effects
MH  - Immunomodulating Agents/*pharmacology
MH  - Immunomodulation/drug effects
MH  - Inflammation/*drug therapy/immunology
MH  - Lipopolysaccharides
MH  - Lung/*drug effects/immunology
MH  - Lung Diseases/drug therapy/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Organ Culture Techniques
OTO - NOTNLM
OT  - Ex vivo models
OT  - Immunomodulatory therapeutics
OT  - Lung inflammation
OT  - Precision cut lung slices
EDAT- 2021/07/01 06:00
MHDA- 2022/01/12 06:00
CRDT- 2021/06/30 12:28
PHST- 2021/04/24 00:00 [received]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/07/01 06:00 [pubmed]
PHST- 2022/01/12 06:00 [medline]
PHST- 2021/06/30 12:28 [entrez]
AID - 10.1007/s00204-021-03096-y [pii]
AID - 10.1007/s00204-021-03096-y [doi]
PST - ppublish
SO  - Arch Toxicol. 2021 Aug;95(8):2871-2877. doi: 10.1007/s00204-021-03096-y. Epub 
      2021 Jun 30.