PMID- 10418824
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20131121
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 79
IP  - 7
DP  - 1999 Jul
TI  - Intracellular glutathione redox status modulates MCP-1 expression in pulmonary 
      granulomatous vasculitis.
PG  - 837-47
AB  - A wide spectrum of human lung diseases is characterized by the presence of 
      granulomas. Although understanding of the pathways leading to their development 
      remains incomplete, data from in vitro studies suggest that neutrophils, 
      monocytes, and their secreted products (eg, hydrogen peroxide, H2O2) influence 
      the pathogenesis of pulmonary granulomatous disease through the regulation of 
      local chemokine and cytokine production. Using a well-characterized rat model of 
      glucan-induced pulmonary granulomatous vasculitis, we sought to determine the 
      role of intracellular glutathione (GSH) redox status in the expression of 
      monocyte chemoattractant protein-1 (MCP-1). Previous studies have revealed that 
      vascular wall MCP-1 expression is obligatory for granuloma development and that 
      both neutrophils and hydrogen peroxide are required for MCP-1 induction. Because 
      in vitro expression of MCP-1 is in part mediated by the redox-sensitive 
      transcription factors nuclear factor-kappa B (NF-kappaB) and activator protein-1 
      (AP-1), we studied their activation as a function of varying intracellular GSH 
      redox status in the pathogenesis of glucan-induced pulmonary granulomatosis. 
      Infusion of particulate yeast cell wall glucan into rats resulted in a rapid 
      decrease in intracellular GSH concentrations which was accompanied by the 
      activation of NF-kappaB and AP-1. The pattern of AP-1 and NF-kappaB activation in 
      turn correlated temporally with the expression of MCP-1. Administration of 
      L-buthionine-S, R-sulfoximine, a specific inhibitor of gamma-glutamyl cysteine 
      synthetase, resulted in a significant reduction in intracellular GSH pools. GSH 
      depletion resulted in a more than 100% increase in pulmonary MCP-1 concentrations 
      and increased cytosolic to nuclear translocation of NF-kappaB while having no 
      effect on AP-1 levels. These observations suggest that in the pathogenesis of 
      pulmonary granulomatous disease, intracellular glutathione redox status modulates 
      the expression of MCP-1 through redox-sensitive transcription factors.
FAU - Desai, A
AU  - Desai A
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor 
      48109-0602, USA.
FAU - Huang, X
AU  - Huang X
FAU - Warren, J S
AU  - Warren JS
LA  - eng
GR  - HL-48287/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  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glucans)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*biosynthesis
MH  - Disease Models, Animal
MH  - Glucans/toxicity
MH  - Glutathione/*metabolism
MH  - Lung Diseases/chemically induced/*metabolism
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Oxidation-Reduction
MH  - Rats
MH  - Rats, Long-Evans
MH  - Transcription Factor AP-1/metabolism
MH  - Vasculitis/chemically induced/*metabolism
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1999 Jul;79(7):837-47.