Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: Effect of ozone-induced SP-A oxidation

Weixiong Huang, Guirong Wang, David Phelps, Hamid Al-Mondhiry, Joanna Floros

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Abstract

Surfactant protein A (SP-A) plays a role in innate host defense. Human SP-A is encoded by two functional genes (SP-A1 and SP-A2), and several alleles have been characterized for each gene. We assessed the effect of in vitro expressed human SP-A genetic variants, on TNF-α and IL-8 production by THP-1 cells in the presence of bleomycin, either before or after ozone-induced oxidation of the variants. The oligomerization of SP-A variants was also examined. We found 1) cytokine levels induced by SP-A2 (1A, 1A0) were significantly higher than those by SP-A1 (6A2, 6A4) in the presence of bleomycin. 2) In the presence of bleomycin, ozone-induced oxidation significantly decreased the ability of 1A and 1A/6A4, but not of 6A4, to stimulate TNF-α production. 3) The synergistic effect of bleomycin/SP-A, either before or after oxidation, can be inhibited to the level of bleomycin alone by surfactant lipids. 4) Differences in oligomerization were also observed between SP-A1 and SP-A2. The results indicate that differences among SP-A variants may partly explain the individual variability of pulmonary complications observed during bleomycin chemotherapy and/or in an environment that may promote protein oxidation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume286
Issue number3 30-3
StatePublished - Mar 1 2004

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Pulmonary Surfactant-Associated Protein A
Ozone
Bleomycin
Cytokines
varespladib methyl
Interleukin-8
Surface-Active Agents
Genes
Alleles
Lipids
Drug Therapy
Lung
indium-bleomycin

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

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title = "Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: Effect of ozone-induced SP-A oxidation",
abstract = "Surfactant protein A (SP-A) plays a role in innate host defense. Human SP-A is encoded by two functional genes (SP-A1 and SP-A2), and several alleles have been characterized for each gene. We assessed the effect of in vitro expressed human SP-A genetic variants, on TNF-α and IL-8 production by THP-1 cells in the presence of bleomycin, either before or after ozone-induced oxidation of the variants. The oligomerization of SP-A variants was also examined. We found 1) cytokine levels induced by SP-A2 (1A, 1A0) were significantly higher than those by SP-A1 (6A2, 6A4) in the presence of bleomycin. 2) In the presence of bleomycin, ozone-induced oxidation significantly decreased the ability of 1A and 1A/6A4, but not of 6A4, to stimulate TNF-α production. 3) The synergistic effect of bleomycin/SP-A, either before or after oxidation, can be inhibited to the level of bleomycin alone by surfactant lipids. 4) Differences in oligomerization were also observed between SP-A1 and SP-A2. The results indicate that differences among SP-A variants may partly explain the individual variability of pulmonary complications observed during bleomycin chemotherapy and/or in an environment that may promote protein oxidation.",
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T1 - Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells

T2 - Effect of ozone-induced SP-A oxidation

AU - Huang, Weixiong

AU - Wang, Guirong

AU - Phelps, David

AU - Al-Mondhiry, Hamid

AU - Floros, Joanna

PY - 2004/3/1

Y1 - 2004/3/1

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