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Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage
- Source :
- The American Journal of Physiology. May, 2007, Vol. 292 Issue 5, pL1227, 6 p.
- Publication Year :
- 2007
-
Abstract
- Although studies have shown that 17[beta]-estradiol ([E.sub.2]) prevents neutrophil infiltration and organ damage following trauma-hemorrhage, the mechanism by which [E.sub.2] inhibits neutrophil transmigration remains unknown. Macrophage migration inhibitory factor (MIF) is thought to play a central role in exacerbation of inflammation and is associated with lung injury. MIF regulates the inflammatory response through modulation of Toll-like receptor 4 (TLR4). Activation of TLR4 results in the release of proinflammatory cytokines and chemokines, which induce neutrophil infiltration and subsequent tissue damage. We hypothesized that E2 mediates its salutary effects in the lung following trauma-hemorrhage via negative regulation of MIF and modulation of TLR4 and cytokine-induced chemotaxis. C3H/HeOuJ mice were subjected to trauma-hemorrhage (mean blood pressure 35 [+ or -] 5 mmHg for ~90 min, then resuscitation) or sham operation. Mice received vehicle, [E.sub.2], or [E.sub.2] in combination with recombinant mouse MIF protein (rMIF). Trauma-hemorrhage increased lung MIF and TLR4 protein levels as well as lung and systemic levels of cytokines/chemokines. Treatment of animals with [E.sub.2] following trauma-hemorrhage prevented these changes. However, administration of rMIF protein with [E.sub.2] abolished the [E.sub.2]-mediated decrease in lung TLR4 levels, lung and plasma levels of IL-6, TNF-[alpha], monocyte chemoattractant protein-1, and keratinocyte-derived chemokine (KC). Administration of rMIF protein also prevented [E.sub.2]-mediated reduction in neutrophil influx and tissue damage in the lungs following trauma-hemorrhage. These results suggest that the protective effects of [E.sub.2] on lung injury following trauma-hemorrhage are mediated via downregulation of lung MIF and TLR4-induced cytokine/chemokine production. hemorrhagic shock; 17[beta]-estradiol; Toll-like receptor 4; myeloperoxidase; cytokines; chemokines doi:10.1152/ajplung.00479.2006
Details
- Language :
- English
- ISSN :
- 00029513
- Volume :
- 292
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.164253707