PMID- 11943661
OWN - NLM
STAT- MEDLINE
DCOM- 20020509
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 282
IP  - 5
DP  - 2002 May
TI  - Activation of NF-kappaB-dependent gene expression by silica in lungs of 
      luciferase reporter mice.
PG  - L968-75
AB  - Occupational exposure to crystalline silica is associated with the development of 
      pulmonary inflammation and silicosis, yet how silica initiates pulmonary fibrosis 
      and which cell types are involved are unclear. In studies here, we hypothesized 
      that silica particles interact initially with pulmonary epithelial cells and 
      alveolar macrophages (AMs) to cause transcriptional activation of nuclear factor 
      (NF)-kappaB-regulated genes encoding inflammatory cytokines. Exposure of 
      NF-kappaB luciferase reporter mice intratracheally to silica or 
      lipopolysaccharide (LPS), but not the nonfibrogenic particle titanium dioxide 
      (TiO(2)), increased immunoreactivity of luciferase protein in bronchiolar 
      epithelial cells and AMs. Ribonuclease protection assays revealed significant (P 
      < or = 0.05) increases in mRNA levels of inducible nitric oxide synthase, tumor 
      necrosis factor-alpha, macrophage inflammatory protein-2, macrophage chemotactic 
      protein-1 (MCP-1), interferon-gamma, interleukin (IL)-6, and IL-12 in lung 
      homogenates of reporter mice after exposures to silica or LPS. Immunoreactivity 
      of MCP-1 in these animals was localized to AMs and epithelial cells. These data 
      are the first to show activation of NF-kappaB in situ by fibrogenic particles in 
      pulmonary epithelial cells and AMs. Increased expression of NF-kappaB-related 
      inflammatory cytokines by these cell types, which first encounter silica after 
      inhalation, may be critical to the initiation of silica-associated lung diseases, 
      thus providing a rationale for focusing on NF-kappaB in preventive and 
      therapeutic strategies.
FAU - Hubbard, Andrea K
AU  - Hubbard AK
AD  - Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269, 
      USA.
FAU - Timblin, Cynthia R
AU  - Timblin CR
FAU - Shukla, Arti
AU  - Shukla A
FAU - Rincon, Mercedes
AU  - Rincon M
FAU - Mossman, Brooke T
AU  - Mossman BT
LA  - eng
GR  - R01 ES/HL-09213/ES/NIEHS NIH HHS/United States
GR  - R01 HL-39469/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 15FIX9V2JP (titanium dioxide)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - D1JT611TNE (Titanium)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Bronchi/cytology/immunology
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/genetics
MH  - Gene Expression/drug effects/immunology
MH  - Genes, Reporter
MH  - Lipopolysaccharides
MH  - Luciferases/genetics
MH  - Lung/*physiology
MH  - Macrophages, Alveolar/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - NF-kappa B/*metabolism
MH  - Pneumonia/chemically induced/immunology/physiopathology
MH  - RNA, Messenger/analysis
MH  - Respiratory Mucosa/cytology/immunology/metabolism
MH  - Silicon Dioxide/*pharmacology
MH  - Silicosis/immunology/*physiopathology
MH  - Titanium/pharmacology
EDAT- 2002/04/12 10:00
MHDA- 2002/05/10 10:01
CRDT- 2002/04/12 10:00
PHST- 2002/04/12 10:00 [pubmed]
PHST- 2002/05/10 10:01 [medline]
PHST- 2002/04/12 10:00 [entrez]
AID - 10.1152/ajplung.00327.2001 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L968-75. doi: 
      10.1152/ajplung.00327.2001.