PMID- 21679503
OWN - NLM
STAT- MEDLINE
DCOM- 20111101
LR  - 20181201
IS  - 1945-8932 (Electronic)
IS  - 1945-8932 (Linking)
VI  - 25
IP  - 2
DP  - 2011 Mar-Apr
TI  - Heparin inhibits mucus hypersecretion in airway epithelial cells.
PG  - 69-74
LID - 10.2500/ajra.2011.25.3562 [doi]
AB  - BACKGROUND: Heparin is one of the most important anticoagulant drugs. It has been 
      known that heparin also possesses anti-inflammatory activities. Mucus 
      hypersecretion is an important characteristic of airway inflammation. However, 
      little is known about the regulatory effects of heparin on mucus hypersecretion 
      in airway epithelial cells. To elucidate the anti-inflammatory function of 
      heparin in airway epithelial cells, we examined the in vivo effects of heparin on 
      mucus hypersecretion and neutrophil infiltration in rat nasal epithelium. We also 
      examined the in vitro effects of heparin on mucin production and IL-8 secretion 
      from cultured human airway epithelial cells. METHODS: We induced hypertrophic and 
      metaplastic changes of goblet cells in rat nasal epithelium by intranasal 
      lipopolysaccharide (LPS) instillation. The effects of intranasal instillation 
      with heparin on mucus production and neutrophil infiltration were examined. in 
      vitro effects of heparin on airway epithelial cells were examined using cultured 
      NCI-H292 cells. Mucus secretion was evaluated by enzyme-linked immunosorbent 
      assay using an anti-MUC5AC monoclonal antibody. RESULTS: Intranasal instillation 
      with unfractionated heparin (UFH; 100 IU/0.1 mL) or low molecular weight heparin 
      (LMWH; 100 IU/0.1 mL) at 30 minutes before LPS instillation significantly 
      inhibited LPS-induced mucus production and neutrophil infiltration in rat nasal 
      epithelium. UFH or LMWH inhibited tumor necrosis factor alpha (10 ng/mL)-induced 
      secretion of MUC5AC and IL-8 from NCI-H292 cells in a dose-dependent manner 
      (0.01-10 IU/mL). MUC5AC mRNA expression was also significantly inhibited. 
      CONCLUSION: These results indicate that heparin inhibits airway mucus 
      hypersecretion in airway epithelial cells directly and indirectly through the 
      suppression of IL-8 secretion and neutrophil infiltration.
FAU - Ogawa, Takao
AU  - Ogawa T
AD  - Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, 
      Japan. takao971@belle.shiga-med.ac.jp
FAU - Shimizu, Shino
AU  - Shimizu S
FAU - Tojima, Ichiro
AU  - Tojima I
FAU - Kouzaki, Hideaki
AU  - Kouzaki H
FAU - Shimizu, Takeshi
AU  - Shimizu T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Rhinol Allergy
JT  - American journal of rhinology & allergy
JID - 101490775
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Mucins)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Anti-Inflammatory Agents/*administration & dosage/adverse effects/pharmacology
MH  - Cell Line
MH  - Heparin/*administration & dosage/adverse effects/pharmacology
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/administration & dosage
MH  - Mucins/metabolism
MH  - Mucus
MH  - Nasal Mucosa/*drug effects/metabolism/pathology
MH  - Pneumonia/chemically induced/*drug therapy/pathology/physiopathology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - *Secretory Pathway/drug effects
EDAT- 2011/06/18 06:00
MHDA- 2011/11/02 06:00
CRDT- 2011/06/18 06:00
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2011/11/02 06:00 [medline]
AID - 10.2500/ajra.2011.25.3562 [doi]
PST - ppublish
SO  - Am J Rhinol Allergy. 2011 Mar-Apr;25(2):69-74. doi: 10.2500/ajra.2011.25.3562.