Tlr2 on bone marrow and non-bbone marrow derived cells regulates inflammation and organ injury in cooperation with Tlr4 during resuscitated hemorrhagic shock
Background: - Although the role of TLR4 in driving inflammation and organ injury after hemorrhagic shock and resuscitation (H/R) is well established, the role of TLR2—another receptor for damage-associated molecular pattern (DAMP) molecules—is not. In this study, we used a combination of TL...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
5 May 2016
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| In: |
Shock
Year: 2016, Volume: 46, Issue: 5, Pages: 519-526$p8 |
| ISSN: | 1540-0514 |
| DOI: | 10.1097/SHK.0000000000000650 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/SHK.0000000000000650 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/shockjournal/Fulltext/2016/11000/Tlr2_on_Bone_Marrow_and_Non_Bone_Marrow_Derived.8.aspx 
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| Author Notes: | Sebastian Korff, Patricia Loughran, Changchun Cai, Jie Fan, Greg Elson, Limin Shang, Susana Salgado Pires, Yi Shan Lee, Jesse Guardado, Melanie Scott, and Timothy R. Billiar |
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| 520 | |a Background: - Although the role of TLR4 in driving inflammation and organ injury after hemorrhagic shock and resuscitation (H/R) is well established, the role of TLR2—another receptor for damage-associated molecular pattern (DAMP) molecules—is not. In this study, we used a combination of TLR2−/− and wild type (WT) mice treated with anti-TLR2 and anti-TLR4 neutralizing monoclonal antibodies (mAb) to discern the contribution of TLR2 relative to TLR4 to the systemic inflammatory response in murine H/R. - Material and Methods: - WT mice, TLR2−/−, and WT mice receiving an anti-TLR2 or an anti-TLR4 mAB (given as a pretreatment) were sacrificed at 6 or 20 h post-H/R. Bone marrow TLR2/WT chimeric mice were created to assess the importance of immune and nonimmune cell-associated TLR2. - Results: - TLR2−/− mice subjected to H/R exhibited significantly less liver damage and lower markers of systemic inflammation only at 20 h. Bone marrow chimeric mice using combinations of TLR2−/− mice and WT mice demonstrated that TLR2 on non-bone marrow derived cells played a dominant role in the differences at 20 h. Interestingly, WT mice treated with anti-TLR2 mAB demonstrated a reduction in organ damage and systemic inflammation at both 6 and 20 h following H/R. A combination of anti-TLR2 mAB and anti-TLR4 mAB showed that both receptors drive IP-10 and KC levels and that there is cooperation for increases in IL-6, MIG, and MCP-1 levels between TLR2 and TLR4. - Conclusion: - These data also support the conclusion that TLR2 and TLR4 act in concert as important receptors in the host immune response to H/R. | ||
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| 700 | 1 | |a Cai, Changchun |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fan, Jie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Elson, Greg |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shang, Limin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pires, Susana Salgado |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Scott, Melanie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Billiar, Timothy R. |e VerfasserIn |4 aut | |
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