ArticleMolecular immunology2007
17Beta-estradiol downregulates Kupffer cell TLR4-dependent p38 MAPK pathway and normalizes inflammatory cytokine production following trauma-hemorrhage.
Article in Molecular immunology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
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- Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer.Cell death & disease · 2021Article
- Anti-inflammatory activity of psoralen in human periodontal ligament cells via estrogen receptor signaling pathway.Scientific reports · 2021Article
- 17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection.Clinics (Sao Paulo, Brazil) · 2020Review
- Gender differences in trauma, shock and sepsis.Military Medical Research · 2018Review
- Sexual dimorphism in bacterial infections.Biology of sex differences · 2018Review
- The influence of sex steroid hormones on the response to trauma and burn injury.Burns & trauma · 2017Review
- Lipopolysaccharide induces SBD-1 expression via the P38 MAPK signaling pathway in ovine oviduct epithelial cells.Lipids in health and disease · 2016Article
- Article
- Sex-specific signaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl/6 mice.Biology of sex differences · 2012Article
- The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney.Journal of anesthesia · 2012Review
- Racial disparities and sex-based outcomes differences after severe injury.Journal of the American College of Surgeons · 2012Article
- Article
- Involvement of toll-like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis.Journal of periodontal research · 2011Article
- Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Trauma-hemorrhage and hypoxia differentially influence kupffer cell phagocytic capacity: role of hypoxia-inducible-factor-1alpha and phosphoinositide 3-kinase/Akt activation.Annals of surgery · 2009Article
- Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications.Biochimica et biophysica acta · 2009Review
- Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?The Journal of surgical research · 2009Article
- Mechanism of the salutary effects of estrogen on kupffer cell phagocytic capacity following trauma-hemorrhage: pivotal role of Akt activation.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- When apoptosis meets autophagy: deciding cell fate after trauma and sepsis.Trends in molecular medicine · 2009Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Although studies have shown that 17beta-estradiol (estradiol) normalized Kupffer cell function following trauma-hemorrhage, the mechanism by which E2 maintains immune function remains unclear. Activation of Toll-like receptor 4 (TLR4) initiates an inflammatory cascade, involving activation of p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappaB (NF-kappaB). This leads to the release of proinflammatory cytokines. Thus, we hypothesized that the salutary effects of estradiol on Kupffer cell function following trauma-hemorrhage are mediated via negative regulation of TLR4-dependent p38 MAPK and NF-kappaB. TLR4 mutant (C3H/HeJ) and wild type (C3H/HeOuJ) mice were subjected to trauma-hemorrhage (mean BP 35+/-5 mmHg approximately 90 min, then resuscitation) or sham operation. Administration of estradiol following trauma-hemorrhage in wild type mice decreased Kupffer cell TLR4 expression as well as prevented the phosphorylation of p38 MAPK and NF-kappaB. This was accompanied by normalization of Kupffer cell production capacities of IL-6, TNF-alpha, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 and the decrease in plasma cytokine levels. In contrast, TLR4 mutant mice did not exhibit the increase in Kupffer cell p38 MAPK and NF-kappaB activation, cytokine production, or the increase in circulating cytokine levels following trauma-hemorrhage. No difference was observed in activation of PI3K among groups. These results suggest that the protective effect of estradiol on Kupffer cell function is mediated via downregulation of TLR4-dependent p38 MAPK and NF-kappaB signaling following trauma-hemorrhage, which prevents the systemic release of cytokines.
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