PUBLICATION
A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation
- Authors
- Oehlers, S.H., Flores, M.V., Hall, C.J., Wang, L., Ko, D.C., Crosier, K.E., Crosier, P.S.
- ID
- ZDB-PUB-161126-3
- Date
- 2017
- Source
- The FEBS journal 284(3): 402-413 (Journal)
- Registered Authors
- Crosier, Kathy, Crosier, Phil, Flores, Maria, Hall, Chris, Oehlers, Stefan
- Keywords
- Colitis, IBD, Inflammation, chemical screen, neuro-immune
- MeSH Terms
-
- Intestines/drug effects
- Intestines/immunology
- Intestines/pathology
- Trinitrobenzenesulfonic Acid
- Crohn Disease/chemically induced
- Crohn Disease/drug therapy*
- Crohn Disease/immunology
- Crohn Disease/pathology
- Embryo, Nonmammalian
- Dysbiosis/chemically induced
- Dysbiosis/drug therapy*
- Dysbiosis/immunology
- Dysbiosis/pathology
- Disease Models, Animal
- Receptors, Cholecystokinin/agonists
- Receptors, Cholecystokinin/genetics
- Receptors, Cholecystokinin/immunology
- Anti-Inflammatory Agents/pharmacology*
- Zebrafish
- Animals
- Gene Expression
- Colitis, Ulcerative/chemically induced
- Colitis, Ulcerative/drug therapy*
- Colitis, Ulcerative/immunology
- Colitis, Ulcerative/pathology
- Immunologic Factors/pharmacology*
- Neutrophils/drug effects
- Neutrophils/immunology
- Neutrophils/pathology
- Dextran Sulfate
- High-Throughput Screening Assays*
- Dopamine Agonists/pharmacology
- Humans
- Receptors, Dopamine/genetics
- Receptors, Dopamine/immunology
- Small Molecule Libraries/pharmacology
- Animals, Genetically Modified
- PubMed
- 27885812 Full text @ FEBS J.
Citation
Oehlers, S.H., Flores, M.V., Hall, C.J., Wang, L., Ko, D.C., Crosier, K.E., Crosier, P.S. (2017) A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. The FEBS journal. 284(3):402-413.
Abstract
By performing two high-content small molecule screens on DSS- and TNBS-induced zebrafish enterocolitis models of inflammatory bowel disease, we have identified novel anti-inflammatory drugs from the John Hopkins Clinical Compound Library that suppress neutrophilic inflammation. Live imaging of neutrophil distribution was used to assess the level of acute inflammation and concurrently screen for off-target drug effects. Supporting the validity of our screening strategy, most of the anti-inflammatory drug hits were known antibiotics or anti-inflammatory agents. Novel hits included cholecystokinin (CCK) and dopamine receptor agonists. Using a pharmacological approach, we show that while CCK and dopamine receptor agonists alleviate enterocolitis-associated inflammation, receptor antagonists exacerbate inflammation in zebrafish. This work highlights the utility of small molecule screening in zebrafish enterocolitis models as a tool to identify novel bioactive molecules capable of modulating acute inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping