Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Initiation of coagulation by tissue factor (TF) is a potentially powerful regulator of local inflammatory responses. We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation of Escherichia coli lipopolysaccharide (LPS 0111:B4). At the time of injury, rats received one dose of site-inactivated FVIIa (FFR-FVIIa) or saline intravenously. At 0, 6,12, 24, and 48 h after injury, lungs were examined for histologic changes and bronchoalveolar lavage (BAL) was performed to assess protein, lactate dehydrogenase (LDH) activity, cell counts, and cytokine levels. LPS-injured rats treated with FFR-FVIIa showed decreased intra-alveolar inflammation and fibrin deposition by light microscopy compared with untreated rats. This was accompanied by decreased protein leakage (P < 0.0001), LDH activity (P < 0.0001), and local elaboration of interleukin (IL)-1beta, IL-6, and IL-10 (all P < 0.0001), but not tumor necrosis factor (TNF)-alpha. Protection was associated with reduction of TF mRNA expression in whole lung, but not with changes in nuclear translocation of nuclear factor (NF)-kappaB. FFR-FVIIa given 6 h after LPS afforded equivalent lung protection. Therefore, blockade of TF-FVIIa complex protects the lung from injury by LPS in part by reducing local expression of proinflammatory cytokines and may offer promise for therapy of acute lung injury.
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PMID:Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. 1203 63

Adenosine monophosphate-activated protein kinase (AMPK) mediates metabolic responses of muscle to exercise and is involved in improvement of insulin resistance by endurance exercise. Recent studies have suggested that the renin-angiotensin system might negatively modulate insulin-mediated actions, but there has been little investigation of the correlation between the renin-angiotensin system and AMPK. To determine this correlation, we performed studies with glucose clamp in vivo, and glucose uptake by skeletal muscle ex vivo using 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). Six-week-old male Sprague-Dawley rats were fed standard chow (standard-diet rats; SD) or fructose-rich chow (fructose-fed rats; FFR) for 6 weeks. At the age of 12 weeks, SD and FFR were treated by oral gavage, either with angiotensin II (Ang II) receptor blockade (ARB; valsartan 30 mg/kg) or vehicle. Thirty minutes after the treatment, we performed glucose clamp studies to measure glucose infusion rates during infusion of insulin (GIR(I)) and of AICAR (GIR(A)), which stimulates AMPK, and studied the effect of ARB on either GIR(I) or GIR(A). In an ex vivo study, we used bilateral fresh soleus muscles from 3-week-old male Sprague-Dawley rats to examine the glucose uptake (measured by (3)H-2-deoxyglucose uptake) of one side of soleus muscle incubated with AICAR with or without Ang II, or with tumor necrosis factor-alpha, in comparison with that of the other (untreated control) side of the muscle. Blood pressure of FFR was significantly higher than that of SD rats. GIR(I) was significantly lower in FFR than in SD, and treatment with ARB did not change GIR(I). GIR(A) of FFR was significantly lower than that of SD, but GIR(A) of FFR treated with ARB was significantly increased compared with that of FFR treated with vehicle. In the ex vivo study, incubation with AICAR significantly increased glucose uptake of soleus muscles, Ang II significantly decreased AICAR-activated glucose uptake in a dose-dependent manner, and ARB canceled the effect of Ang II. The results suggest that acute inhibition of the angiotensin 1 receptor improves glucose metabolism via not insulin but AMPK pathway through the angiotensin 1 receptor in FFR.
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PMID:Angiotensin II inhibits glucose uptake of skeletal muscle via the adenosine monophosphate-activated protein kinase pathway. 2040 57