Lipopolysaccharide binding protein inhibitory peptide alters hepatic inflammatory response post-hemorrhagic shock
| Autor: | Jean A Nemzek-Hamlin, Jill Bayliss, Grace L. Su, Tara M Cotroneo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Inflammatory response Immunology Chromosomal translocation Shock Hemorrhagic Pharmacology Microbiology Cell Line Hepatitis Mice medicine Animals Humans RNA Messenger Molecular Biology biology Chemistry RNA Interferon-beta Cell Biology Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal Infectious Diseases Gene Expression Regulation Liver Cell culture Shock (circulatory) Myeloid Differentiation Factor 88 Hemorrhagic shock TLR4 biology.protein Cytokines medicine.symptom Peptides Lipopolysaccharide binding protein Signal Transduction |
| Zdroj: | Innate Immunity. 18:866-875 |
| ISSN: | 1753-4267 1753-4259 |
| DOI: | 10.1177/1753425912444641 |
| Popis: | Translocation of microorganisms and endotoxin (LPS) across the gastrointestinal mucosa may exacerbate the inflammatory response and potentiate hepatic injury associated with hemorrhagic shock. Lipopolysaccharide binding protein (LBP) augments LPS signaling through TLR4. In addition, evidence suggests that TLR4-mediated injury in liver ischemia/reperfusion occurs through the IRF-3/MyD88 independent pathway. We hypothesized that administration of LBP inhibiting peptide, LBPK95A, given at the time of resuscitation would reduce liver inflammation and injury in a murine model of hemorrhagic shock by limiting LPS-induced activation of the MyD88 independent pathway. Hemorrhagic shock was induced in male, C57BL/6 mice; a mean arterial blood pressure of 35 mmHg was maintained for 2.5 h. LBPK95A peptide or equal volume Lactated Ringer’s solution was administered followed by fluid resuscitation. Mice were sacrificed at 2 and 6 h post-resuscitation. At 2 h, liver mRNA levels revealed a significant reduction in IFN-β, a cytokine produced via the MyD88 independent pathway, with LBPK95A treatment. However, mRNA levels of TNF-α, a cytokine associated with the MyD88 dependent pathway, were unaffected by treatment. The LBP inhibitory peptide did selectively reduce activation of TLR4 signaling via the IRF-3/MyD88 independent pathway. These results suggest that LBP promotes cytokine production through the MyD88 independent pathway during hemorrhagic shock. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|