PMID- 21087909
OWN - NLM
STAT- MEDLINE
DCOM- 20110613
LR  - 20211020
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 119
IP  - 3
DP  - 2011 Mar
TI  - Diesel particulate matter induces receptor for advanced glycation end-products 
      (RAGE) expression in pulmonary epithelial cells, and RAGE signaling influences 
      NF-kappaB-mediated inflammation.
PG  - 332-6
LID - 10.1289/ehp.1002520 [doi]
AB  - BACKGROUND: Receptors for advanced glycation end-products (RAGE) are cell-surface 
      receptors expressed by alveolar type I (ATI) epithelial cells and are implicated 
      in mechanisms of alveolar development and sustained pulmonary inflammation. 
      OBJECTIVES: In the present study, we tested the hypothesis that diesel 
      particulate matter (DPM) up-regulates RAGE in rat ATI-like R3/1 cells and human 
      primary small airway epithelial cells (SAECs), leading to an inflammatory 
      response. METHODS AND RESULTS: Using real-time reverse transcriptase polymerase 
      chain reaction and immunoblotting, we found that RAGE mRNA and protein are 
      up-regulated in cells exposed to DPM for 2 hr. Use of a luciferase reporter 
      containing nuclear factor-kappaB (NF-kappaB) response elements revealed decreased NF-kappaB 
      activation in cells transfected with small interfering RNA (siRNA) for RAGE 
      (siRAGE) before DPM exposure compared with cells transfected with scrambled 
      control siRNA (siControl). In addition, immunostaining revealed diminished 
      nuclear translocation of NF-kappaB in DPM-exposed cells transfected with siRAGE 
      compared with cells transfected with siControl before DPM stimulation. 
      Enzyme-linked immunosorbent assay demonstrated that in R3/1 cells DPM induced 
      secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), 
      two cytokines induced by NF-kappaB and associated with leukocyte chemotaxis during an 
      inflammatory response. Incorporating siRAGE was sufficient to significantly 
      decrease DPM-induced MCP-1 and IL-8 secretion compared with cells transfected 
      with siControl. CONCLUSIONS: These data offer novel insights into potential 
      mechanisms whereby RAGE influences pulmonary inflammation exacerbated by DPM 
      exposure. Further research may demonstrate that molecules involved in RAGE 
      signaling are potential targets in lessening the degree of particulate 
      matter-induced exacerbations of inflammatory lung disease.
FAU - Reynolds, Paul R
AU  - Reynolds PR
AD  - Department of Physiology and Developmental Biology, Brigham Young University, 
      Provo, Utah 84602, USA. paul_reynolds@byu.edu
FAU - Wasley, Karisa M
AU  - Wasley KM
FAU - Allison, Camille H
AU  - Allison CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101118
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Air Pollutants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Particulate Matter)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Vehicle Emissions)
SB  - IM
CIN - Environ Health Perspect. 2011 Mar;119(3):a132. PMID: 21356633
MH  - Air Pollutants/*toxicity
MH  - Alveolar Epithelial Cells/drug effects/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Epithelial Cells/drug effects/metabolism
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Particulate Matter/toxicity
MH  - Pneumonia/chemically induced/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/genetics/*metabolism
MH  - Vehicle Emissions/*toxicity
PMC - PMC3059995
EDAT- 2010/11/20 06:00
MHDA- 2011/06/15 06:00
PMCR- 2011/03/01
CRDT- 2010/11/20 06:00
PHST- 2010/06/03 00:00 [received]
PHST- 2010/11/18 00:00 [accepted]
PHST- 2010/11/20 06:00 [entrez]
PHST- 2010/11/20 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - ehp-119-332 [pii]
AID - 10.1289/ehp.1002520 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2011 Mar;119(3):332-6. doi: 10.1289/ehp.1002520. Epub 
      2010 Nov 18.