PMID- 10562299
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 10
DP  - 1999 Nov
TI  - Allergen-induced IL-9 directly stimulates mucin transcription in respiratory
      epithelial cells.
PG  - 1375-82
AB  - A hallmark of asthma is mucin overproduction, a condition that contributes to
      airway obstruction. The events responsible for mucin overproduction are not known
      but are thought to be associated with mediators of chronic inflammation. Others
      have shown that T-helper 2 (Th2) lymphocytes are required for mucous cell
      metaplasia, which then leads to mucin overproduction in animal models of allergy.
      We hypothesized that Th2 cell mediators are present in asthmatic airway fluid and
      directly stimulate mucin synthesis in airway epithelial cells. Results in
      cultured airway epithelial cells showed that samples of asthmatic fluid
      stimulated mucin (MUC5AC) synthesis severalfold more potently than non-asthmatic 
      fluid. Consistent with this, lavage fluid from the airways of allergen-challenged
      dogs stimulated mucin synthesis severalfold more potently than that from
      non-allergen-challenged dogs. Fractionation of dog samples revealed 2 active
      fractions at <10 kDa and 30-100 kDa. Th2 cytokines in these molecular weight
      ranges are IL-9 (36 kDa), IL-5 (56 kDa), and IL-13 (10 kDa). Antibody blockade of
      ligand-receptor interaction for IL-9 (but not IL-5 or IL-13) inhibited mucin
      stimulation by dog airway fluid. Furthermore, recombinant IL-9, but not IL-5 or
      IL-13, stimulated mucin synthesis. These results indicate that IL-9 may account
      for as much as 50-60% of the mucin-stimulating activity of lung fluids in
      allergic airway disease.
FAU - Longphre, M
AU  - Longphre M
AD  - Department of Anatomy and Cardiovascular Research Institute, School of Medicine, 
      University of California-San Francisco, San Francisco, California 94143, USA.
      longphrm@bms.com
FAU - Li, D
AU  - Li D
FAU - Gallup, M
AU  - Gallup M
FAU - Drori, E
AU  - Drori E
FAU - Ordonez, C L
AU  - Ordonez CL
FAU - Redman, T
AU  - Redman T
FAU - Wenzel, S
AU  - Wenzel S
FAU - Bice, D E
AU  - Bice DE
FAU - Fahy, J V
AU  - Fahy JV
FAU - Basbaum, C
AU  - Basbaum C
LA  - eng
GR  - P01 HL024136/HL/NHLBI NIH HHS/United States
GR  - P01HL24136/HL/NHLBI NIH HHS/United States
GR  - R01HL43762/HL/NHLBI NIH HHS/United States
GR  - R01HL61662/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Allergens)
RN  - 0 (Cytokines)
RN  - 0 (IL9R protein, human)
RN  - 0 (Interleukin-9)
RN  - 0 (Interleukins)
RN  - 0 (MUC5AC protein, human)
RN  - 0 (Muc5ac protein, mouse)
RN  - 0 (Mucin 5AC)
RN  - 0 (Mucins)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-9)
RN  - 0 (Recombinant Proteins)
SB  - AIM
SB  - IM
SB  - X
MH  - Adult
MH  - *Allergens
MH  - Animals
MH  - Asthma/immunology/metabolism/pathology/*physiopathology
MH  - Bronchi/cytology/pathology
MH  - Cells, Cultured
MH  - Cytokines/analysis
MH  - Dogs
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Interleukin-9/genetics/*physiology
MH  - Interleukins/analysis/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mucin 5AC
MH  - Mucins/biosynthesis/*genetics
MH  - Receptors, Interleukin/analysis/genetics
MH  - Receptors, Interleukin-9
MH  - Recombinant Proteins/pharmacology
MH  - Respiratory Mucosa/*immunology/*metabolism/pathology
MH  - Th2 Cells/*immunology
MH  - Trachea/cytology/pathology
MH  - *Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
PMC - PMC409835
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1172/JCI6097 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Nov;104(10):1375-82. doi: 10.1172/JCI6097.