TY - JOUR
T1 - Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells
AU - Oppeltz, Richard F.
AU - Rani, Meenakshi
AU - Zhang, Qiong
AU - Schwacha, Martin G.
N1 - Funding Information:
Support was provided by National Institutes of Health Grant GM079122. These finding were presented in part at the 42nd annual meeting of the American Burn Association in Boston, MA. Authors’ contributions: RFO was responsible for the data analysis, scientific interpretation and drafted the first draft of the manuscript. MR was responsible for experimental design, ELISA analysis, data analysis and scientific interpretation. QZ was responsible for the animal experiments and ELISAs. MGS was responsible for scientific conception, design and helped to draft the manuscript. All authors read and approved the final manuscript.
PY - 2011/9
Y1 - 2011/9
N2 - Burn is associated with profound inflammation and activation of the innate immune system in multiple organ beds, including the lung. Similarly, toll-like receptors (TLR) are associated with innate immune activation. Nonetheless, it is unclear what impact burn has on TLR-induced inflammatory responses in the lung. Methods: Male C57BL/6 mice were subjected to burn (3rd degree, 25% TBSA) or sham procedure and 1, 3 or 7. days thereafter, bronchoalveolar lavage (BAL) fluid was collected and cells were isolated and cultured in vitro with specific TLR agonists as follows: Zymosan (TLR-2), LPS (TLR-4) and CpG-ODN (TLR-9). Supernatants were collected 48. h later and assayed for inflammatory cytokine levels (IL-1β, IL-6, IL-10, IL-17, TNF-α, KC, MCP-1, MIP-1α, MIP-1β and RANTES) by Bioplex. Results: BAL fluid from sham and burn mice did not contain detectable cytokine levels. BAL cells, irrespective of injury, were responsive to TLR-2 and TLR-4 activation. Seven days after burn, TLR-2 and TLR-4 mediated responses by BAL cells were enhanced as evidenced by increased production of IL-6, IL-17, TNF-α, MCP-1, MIP-1β and RANTES. Conclusions: Burn-induced changes in TLR-2 and TLR-4 reactivity may contribute to the development of post-burn complications, such as acute lung injury (ALI) and adult respiratory distress syndrome (ARDS).
AB - Burn is associated with profound inflammation and activation of the innate immune system in multiple organ beds, including the lung. Similarly, toll-like receptors (TLR) are associated with innate immune activation. Nonetheless, it is unclear what impact burn has on TLR-induced inflammatory responses in the lung. Methods: Male C57BL/6 mice were subjected to burn (3rd degree, 25% TBSA) or sham procedure and 1, 3 or 7. days thereafter, bronchoalveolar lavage (BAL) fluid was collected and cells were isolated and cultured in vitro with specific TLR agonists as follows: Zymosan (TLR-2), LPS (TLR-4) and CpG-ODN (TLR-9). Supernatants were collected 48. h later and assayed for inflammatory cytokine levels (IL-1β, IL-6, IL-10, IL-17, TNF-α, KC, MCP-1, MIP-1α, MIP-1β and RANTES) by Bioplex. Results: BAL fluid from sham and burn mice did not contain detectable cytokine levels. BAL cells, irrespective of injury, were responsive to TLR-2 and TLR-4 activation. Seven days after burn, TLR-2 and TLR-4 mediated responses by BAL cells were enhanced as evidenced by increased production of IL-6, IL-17, TNF-α, MCP-1, MIP-1β and RANTES. Conclusions: Burn-induced changes in TLR-2 and TLR-4 reactivity may contribute to the development of post-burn complications, such as acute lung injury (ALI) and adult respiratory distress syndrome (ARDS).
KW - Burn
KW - Cytokines
KW - Lung
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U2 - 10.1016/j.cyto.2011.05.004
DO - 10.1016/j.cyto.2011.05.004
M3 - Article
C2 - 21696980
AN - SCOPUS:79960891059
VL - 55
SP - 396
EP - 401
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 3
ER -