RGD Reference Report - Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4. - Rat Genome Database

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Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4.

Authors: Jame, AJ  Lackie, PM  Cazaly, AM  Sayers, I  Penrose, JF  Holgate, ST  Sampson, AP 
Citation: Jame AJ, etal., Clin Exp Allergy. 2007 Jun;37(6):880-92.
RGD ID: 2313910
Pubmed: PMID:17517102   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-2222.2007.02733.x   (Journal Full-text)

BACKGROUND: Human bronchial epithelial cells synthesize cyclooxygenase and 15-lipoxygenase products, but the 5-lipoxygenase (5-LO) pathway that generates the leukotriene (LT) family of bronchoconstrictor and pro-inflammatory mediators is thought to be restricted to leucocytes. OBJECTIVE: We hypothesized that human bronchial epithelial cells (HBECs) express a complete and active 5-LO pathway for the synthesis of LTB4 and LTC4, either constitutively or after stimulation. METHODS: Flow cytometry, RT-PCR, Western blotting, enzyme immunoassays and reverse-phase high-performance liquid chromatography were used to investigate constitutive and stimulated expression of 5-LO pathway enzymes and the synthesis of LTs B4 and C4 in primary HBECs and in the 16-HBE 14o- cell line. RESULTS: Constitutive mRNA and protein expression for 5-LO, 5-LO-activating protein (FLAP), LTA4 hydrolase and LTC4 synthase were demonstrated in primary HBECs and in the 16-HBE 14o- cell line. In 16-HBE 14o- cells, treatment with calcium ionophore A23187, bradykinin or LPS up-regulated the expression of these enzymes. The up-regulation of 5-LO was blocked by the anti-inflammatory glucocorticoid dexamethasone. Human bronchial epithelial cells were shown to generate bioactive LTs, with primary HBECs generating 11-fold more LTC4 and five-fold more LTB4 than 16-HBE 14o- cells. LT production was enhanced by ionophore treatment and blocked by the FLAP inhibitor MK-886. CONCLUSIONS: Expression of an active and inducible 5-LO pathway in HBEC suggests that damaged or inflamed bronchial epithelium may synthesize LTs that contribute directly to bronchoconstriction and leucocytosis in airway inflammation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Alox5apRatlipoxygenase pathway  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ALOX5Humanleukotriene metabolic pathway  IDA  RGD 
Alox5Mouseleukotriene metabolic pathway  ISOALOX5 (Homo sapiens) RGD 
Alox5Ratleukotriene metabolic pathway  ISOALOX5 (Homo sapiens) RGD 
LTA4HHumanleukotriene metabolic pathway  IDA  RGD 
LTC4SHumanleukotriene metabolic pathway  IDA  RGD 
Lta4hMouseleukotriene metabolic pathway  ISOLTA4H (Homo sapiens) RGD 
Lta4hRatleukotriene metabolic pathway  ISOLTA4H (Homo sapiens) RGD 
Ltc4sRatleukotriene metabolic pathway  ISOLTC4S (Homo sapiens) RGD 
Ltc4sMouseleukotriene metabolic pathway  ISOLTC4S (Homo sapiens) RGD 
ALOX5Humanlipoxygenase mediated pathway of arachidonic acid metabolism  IDA  RGD 
ALOX5APHumanlipoxygenase mediated pathway of arachidonic acid metabolism  IDA  RGD 
Alox5Ratlipoxygenase mediated pathway of arachidonic acid metabolism  ISOALOX5 (Homo sapiens) RGD 
Alox5Mouselipoxygenase mediated pathway of arachidonic acid metabolism  ISOALOX5 (Homo sapiens) RGD 
Alox5apMouselipoxygenase mediated pathway of arachidonic acid metabolism  ISOALOX5AP (Homo sapiens) RGD 
Alox5apRatlipoxygenase mediated pathway of arachidonic acid metabolism  ISOALOX5AP (Homo sapiens) RGD 
LTA4HHumanlipoxygenase mediated pathway of arachidonic acid metabolism  IDA  RGD 
LTC4SHumanlipoxygenase mediated pathway of arachidonic acid metabolism  IDA  RGD 
Lta4hRatlipoxygenase mediated pathway of arachidonic acid metabolism  ISOLTA4H (Homo sapiens) RGD 
Lta4hMouselipoxygenase mediated pathway of arachidonic acid metabolism  ISOLTA4H (Homo sapiens) RGD 
Ltc4sRatlipoxygenase mediated pathway of arachidonic acid metabolism  ISOLTC4S (Homo sapiens) RGD 
Ltc4sMouselipoxygenase mediated pathway of arachidonic acid metabolism  ISOLTC4S (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Alox5  (arachidonate 5-lipoxygenase)
Alox5ap  (arachidonate 5-lipoxygenase activating protein)
Lta4h  (leukotriene A4 hydrolase)
Ltc4s  (leukotriene C4 synthase)

Genes (Mus musculus)
Alox5  (arachidonate 5-lipoxygenase)
Alox5ap  (arachidonate 5-lipoxygenase activating protein)
Lta4h  (leukotriene A4 hydrolase)
Ltc4s  (leukotriene C4 synthase)

Genes (Homo sapiens)
ALOX5  (arachidonate 5-lipoxygenase)
ALOX5AP  (arachidonate 5-lipoxygenase activating protein)
LTA4H  (leukotriene A4 hydrolase)
LTC4S  (leukotriene C4 synthase)


Additional Information