title: HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation.
abstract: BACKGROUND
  The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis.
  
  
  METHODS
  The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge.
  
  
  RESULTS
  We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen.
  
  
  CONCLUSIONS
  These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation.
authors: Hospital Infantil de Mexico, Federico Gomez, Unidad de Investigacion en Enfermedades Oncologicas, Dr, Marquez No 262, Col, Doctores, Delegacion Cuahutemos, Mexico City CP 06720, Mexico.
authors: Guillermina J
authors: GJ
authors: Baay-Guzman
authors: Ilona G
authors: IG
authors: Bebenek
authors: Michelle
authors: M
authors: Zeidler
authors: Rogelio
authors: R
authors: Hernandez-Pando
authors: Mario I
authors: MI
authors: Vega
authors: Eduardo A
authors: EA
authors: Garcia-Zepeda
authors: Gabriela
authors: G
authors: Antonio-Andres
authors: Benjamin
authors: B
authors: Bonavida
authors: Marc
authors: M
authors: Riedl
authors: Eric
authors: E
authors: Kleerup
authors: Donald P
authors: DP
authors: Tashkin
authors: Oliver
authors: O
authors: Hankinson
authors: Sara
authors: S
authors: Huerta-Yepez
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012130:Respiratory Hypersensitivity / Q000378:metabolism / Q000473:pathology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit