Document Detail


IL-17A induces signal transducers and activators of transcription-6-independent airway mucous cell metaplasia.
MedLine Citation:
PMID:  23392574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mucous cell metaplasia is a hallmark of asthma, and may be mediated by signal transducers and activators of transcription (STAT)-6 signaling. IL-17A is increased in the bronchoalveolar lavage fluid of patients with severe asthma, and IL-17A also increases mucus production in airway epithelial cells. Asthma therapeutics are being developed that inhibit STAT6 signaling, but the role of IL-17A in inducing mucus production in the absence of STAT6 remains unknown. We hypothesized that IL-17A induces mucous cell metaplasia independent of STAT6, and we tested this hypothesis in two murine models in which increased IL-17A protein expression is evident. In the first model, ovalbumin (OVA)-specific D011.10 Th17 cells were adoptively transferred into wild-type (WT) or STAT6 knockout (KO) mice, and the mice were challenged with OVA or PBS. WT-OVA and STAT6 KO-OVA mice demonstrated increased airway IL-17A and IL-13 protein expression and mucous cell metaplasia, compared with WT-PBS or STAT6 KO-PBS mice. In the second model, WT, STAT1 KO, STAT1/STAT6 double KO (DKO), or STAT1/STAT6/IL-17 receptor A (RA) triple KO (TKO) mice were challenged with respiratory syncytial virus (RSV) or mock viral preparation, and the mucous cells were assessed. STAT1 KO-RSV mice demonstrated increased airway mucous cell metaplasia compared with WT-RSV mice. STAT1 KO-RSV and STAT1/STAT6 DKO-RSV mice also demonstrated increased mucous cell metaplasia, compared with STAT1/STAT6/IL17RA TKO-RSV mice. We also treated primary murine tracheal epithelial cells (mTECs) from WT and STAT6 KO mice. STAT6 KO mTECs showed increased periodic acid-Schiff staining with IL-17A but not with IL-13. Thus, asthma therapies targeting STAT6 may increase IL-17A protein expression, without preventing IL-17A-induced mucus production.
Authors:
Dawn C Newcomb; Madison G Boswell; Taylor P Sherrill; Vasiliy V Polosukhin; Kelli L Boyd; Kasia Goleniewska; Steven L Brody; Jay K Kolls; Kenneth B Adler; R Stokes Peebles
Related Documents :
24193164 - Inhibition of matrix metalloproteinases-2/-9 transiently reduces pre-oligodendrocyte lo...
12443244 - Different scaling behaviors of commodity spot and future prices.
24140924 - Local inflammatory reaction induced by scolopendra viridicornis centipede venom in mice.
24534954 - Hexane extracts of polygonum multiflorum improve tissue and functional outcome followin...
3062144 - Nutritional aspects of leukocytic cytokines.
14645004 - Mast cell-mediated inflammatory responses require the alpha 2 beta 1 integrin.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-04     Completed Date:  2013-08-05     Revised Date:  2014-06-16    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  711-6     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid / immunology
Female
Interleukin-13 / metabolism
Interleukin-17 / genetics,  metabolism*
Lung / immunology,  pathology
Metaplasia / immunology,  pathology*,  virology
Mice
Mice, Inbred BALB C
Mice, Knockout
Mucus / metabolism*
Neutrophils / metabolism
Ovalbumin / administration & dosage,  immunology
Peptide Fragments / administration & dosage,  immunology
Receptors, Interleukin-17 / genetics,  immunology,  metabolism
Respiratory Syncytial Virus Infections / immunology,  pathology
Respiratory Syncytial Viruses / immunology
STAT1 Transcription Factor / genetics,  metabolism
STAT6 Transcription Factor / genetics,  metabolism*
Th17 Cells / immunology
Transcriptional Activation*
Grant Support
ID/Acronym/Agency:
GM 015431/GM/NIGMS NIH HHS; K12 HD043483/HD/NICHD NIH HHS; K12HD043483-08/HD/NICHD NIH HHS; R01 AI 059108/AI/NIAID NIH HHS; R01 AI 070672/AI/NIAID NIH HHS; R01 HL 090664/HL/NHLBI NIH HHS; R01 HL061271/HL/NHLBI NIH HHS; R21 HL106446/HL/NHLBI NIH HHS; R37 HL 36982/HL/NHLBI NIH HHS; T32 AI007610/AI/NIAID NIH HHS; U19 AI095227/AI/NIAID NIH HHS; U19AI095227/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Il17a protein, mouse; 0/Il17r protein, mouse; 0/Interleukin-13; 0/Interleukin-17; 0/OVA 323-339; 0/Peptide Fragments; 0/Receptors, Interleukin-17; 0/STAT1 Transcription Factor; 0/STAT6 Transcription Factor; 0/Stat1 protein, mouse; 0/Stat6 protein, mouse; 9006-59-1/Ovalbumin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Role of IL-18 in second-hand smoke-induced emphysema.
Next Document:  Hematological abnormalities in severe anorexia nervosa.