[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that men with diabetes have lower testosterone levels than healthy men. However, studies on the correlation between testosterone and diabetes are rare in Korea. We examined the relationship between testosterone deficiency and markers related to diabetes in adult Korean men.
Endocrinology and metabolism (Seoul, Korea). 09/2014; 29(3):300-6.
[Show abstract][Hide abstract] ABSTRACT: Due to the increasing concerns about limited fossil resources and environmental problems, there has been much interest in developing biofuels from renewable biomass. Ethanol is currently used as a major biofuel, as it can be easily produced by existing fermentation technology, but it is not the best biofuel due to its low energy density, high vapor pressure, hygroscopy, and incompatibility with current infrastructure. Higher alcohols, including 1-propanol, 1-butanol, isobutanol, 2-methyl-1-butanol, and 3-methyl-1-butanol, which possess fuel properties more similar to those of petroleum-based fuel, have attracted particular interest as alternatives to ethanol. Since microorganisms isolated from nature do not allow production of these alcohols at high enough efficiencies, metabolic engineering has been employed to enhance their production. Here, we review recent advances in metabolic engineering of microorganisms for the production of higher alcohols.
[Show abstract][Hide abstract] ABSTRACT: Background: Insulin is an important osteotropic hormone, but may be negatively associated with bone mass after adjustment for body mass index in adolescent populations. However, the association between insulin and bone mass in adults remains unclear. Objective: To investigate whether insulin was associated with bone mass in adults, and if so, whether the association was positive or negative. Design: Cross-sectional, using data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009 and the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2006. Setting: Korean and U.S. Population Participants: 7271 KNHANES and 3399 NHANES participants were included. Main Outcome Measures: Anthropometric parameters and bone mass data, fasting glucose and insulin, height, weight, and markers related to insulin resistance. Results: After adjusting for confounding factors, there was an inverse relationship between insulin and total body bone mineral content (BMC) in the KNHANES and NHANES subjects. In a stratified analysis, an association between insulin and bone mass was apparent, especially in the highest homeostatic model of assessment of insulin resistance (HOMA-IR) quartile in the Korean subjects. However, this association was only seen in men in the U.S. subjects. Conclusions: There is an inverse relationship between insulin and total body BMC after adjustment for confounding factors in Korean and U.S. subjects, especially in the insulin-resistant population. This strongly suggests that the adverse influence of insulin on bone mass likely reflects the effects of other factors associated with insulin resistance rather than being a direct action of insulin itself.
The Journal of Clinical Endocrinology and Metabolism 01/2014; · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Escherichia coli XL1-blue strain was metabolically engineered to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] through 2-ketobutyrate, which is generated via citramalate pathway, as a precursor for propionyl-CoA. Two different metabolic pathways were examined for the synthesis of propionyl-CoA from 2-ketobutyrate. The first pathway is composed of the Dickeya dadantii 3937 2-ketobutyrate oxidase or the E. coli pyruvate oxidase mutant (PoxB L253F V380A) for the conversion of 2-ketobutyrate into propionate and the Ralstonia eutropha propionyl-CoA synthetase (PrpE) or the E. coli acetyl-CoA:acetoacetyl-CoA transferase for further conversion of propionate into propionyl-CoA. The second pathway employs pyruvate formate lyase encoded by the E. coli tdcE gene or the Clostridium difficile pflB gene for the direct conversion of 2-ketobutyrate into propionyl-CoA. As the direct conversion of 2-ketobutyrate into propionyl-CoA could not support the efficient production of P(3HB-co-3HV) from glucose, the first metabolic pathway was further examined. When the recombinant E. coli XL1-blue strain equipped with citramalate pathway expressing the E. coli poxB L253F V380A gene and R. eutropha prpE gene together with the R. eutropha PHA biosynthesis genes was cultured in a chemically defined medium containing 20 g/L of glucose as a sole carbon source, P(3HB-co-2.3 mol% 3HV) was produced up to the polymer content of 61.7 wt.%. Moreover, the 3HV monomer fraction in P(3HB-co-3HV) could be increased up to 5.5 mol% by additional deletion of the prpC and scpC genes, which are responsible for the metabolism of propionyl-CoA in host strains.
Applied Microbiology and Biotechnology 10/2013; · 3.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increasing concerns about limited fossil fuels and global environmental problems have focused attention on the need to develop sustainable biofuels from renewable resources. Although microbial production of diesel has been reported, production of another much in demand transport fuel, petrol (gasoline), has not yet been demonstrated. Here we report the development of platform Escherichia coli strains that are capable of producing short-chain alkanes (SCAs; petrol), free fatty acids (FFAs), fatty esters and fatty alcohols through the fatty acyl (acyl carrier protein (ACP)) to fatty acid to fatty acyl-CoA pathway. First, the β-oxidation pathway was blocked by deleting the fadE gene to prevent the degradation of fatty acyl-CoAs generated in vivo. To increase the formation of short-chain fatty acids suitable for subsequent conversion to SCAs in vivo, the activity of 3-oxoacyl-ACP synthase (FabH), which is inhibited by unsaturated fatty acyl-ACPs, was enhanced to promote the initiation of fatty acid biosynthesis by deleting the fadR gene; deletion of the fadR gene prevents upregulation of the fabA and fabB genes responsible for unsaturated fatty acids biosynthesis. A modified thioesterase was used to convert short-chain fatty acyl-ACPs to the corresponding FFAs, which were then converted to SCAs by the sequential reactions of E. coli fatty acyl-CoA synthetase, Clostridium acetobutylicum fatty acyl-CoA reductase and Arabidopsis thaliana fatty aldehyde decarbonylase. The final engineered strain produced up to 580.8 mg l(-1) of SCAs consisting of nonane (327.8 mg l(-1)), dodecane (136.5 mg l(-1)), tridecane (64.8 mg l(-1)), 2-methyl-dodecane (42.8 mg l(-1)) and tetradecane (8.9 mg l(-1)), together with small amounts of other hydrocarbons. Furthermore, this platform strain could produce short-chain FFAs using a fadD-deleted strain, and short-chain fatty esters by introducing the Acinetobacter sp. ADP1 wax ester synthase (atfA) and the E. coli mutant alcohol dehydrogenase (adhE(mut)).
[Show abstract][Hide abstract] ABSTRACT: Short sleep duration has been reported to increase the risk of diabetes. However, the influence of sleep duration on glycemic control in diabetic patients has not been clarified. In this study we evaluated the association between sleep duration and glycemic control in diabetic patients. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010. Sleep duration was classified into five groups: <6, 6, 7, 8, and ≥9 h/day. Fasting blood glucose and HbA1c showed a U-shaped trend according to sleep duration. Sleep duration of 7 h/day had the lowest HbA1c (7.26%) among the subjects (P=0.026). In the older age group (≥65 yr), a sleep duration of 6 h/day was associated with the lowest HbA1c (7.26%). The adjusted odds ratio (OR) with a 95% confidence interval (CI) of worse glycemic control (HbA1c ≥7.0%) in group of sleep duration of ≥9 h/day was 1.48 (1.04-2.13) compared with the group of 7 h/day. This relationship disappeared after adjusting duration of diabetes (OR, 1.38; 95% CI, 0.93-2.03). Our results suggest that sleep duration and glycemic control in diabetic patients has U-shaped relationship which was mainly affected by duration of diabetes.
Journal of Korean medical science 09/2013; 28(9):1334-9. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Occupation affects bone mineral density (BMD); however, only few studies have been published. This study evaluated the effect of working time during a day on BMD. The cross-sectional study involved 18- to 50-year-old people who reported their working time and were measured for BMD using dual-energy X-ray absorptiometry in the Fourth Korea National Health and Nutrition Examination Survey 2009. The time period of work was divided into "daytime" and "other than daytime." The other-than-daytime group included evening time, nighttime, regular shift time, and irregular shift time. Among 3,005 subjects, 2,378 were daytime workers and 627 were other-than-daytime workers. The mean BMD of the total femur and lumbar spine were significantly lower in other-than-daytime workers compared to daytime workers (femur 0.948 vs. 0.966 g/cm(2), respectively, p = 0.001; lumbar spine 0.976 vs. 0.988 g/cm(2), respectively, p = 0.023). The other-than-daytime group had lower levels of serum 25-hydroxyvitamin D than the daytime group (16.3 vs. 17.6 ng/mL, p < 0.001). The proportion of osteopenia (T score < -1.0) was higher in the other-than-daytime than the daytime group (34.3 vs. 29.1 %, p = 0.014). After adjustment for age, sex, socioeconomic status, lifestyle factors, daily intake of calcium, and vitamin D level, the relative risks of osteopenia of regular-shift and irregular-shift workers were significantly higher (1.65, 95 % CI 1.05-2.60; 1.78, 95 % CI 1.09-2.89) than those of daytime workers. These data suggest that other-than-daytime working, especially regular and irregular shift working, is associated with decreased BMD and increased risk for osteopenia in Korean adults.
Calcified Tissue International 08/2013; 93(6). · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the association between suicidal ideation and diabetes in Korean adults with and without depression. Diabetes is a significant risk factor for suicidal ideation and the coexistence of diabetes and depression was associated with a much higher risk of suicidal ideation than with diabetes alone.
Diabetes research and clinical practice 07/2013; · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alendronate is one of the most potent anti-osteoporotic agents for postmenopausal osteoporosis. However, high doses of alendronate cause esophageal irritation, myalgia, gastrointestinal discomfort and decrease of serum calcium level. Recently, Maxmarvil(®) was developed as an enteric-coated tablet containing alendronate (5 mg) and calcitriol (0.5 μg) to minimize these side effects of alendronate. In the present study, we evaluated the pharmacokinetic profile and examined the incidence of unfavorable effects after oral administration of Maxmarvil(®) in Korean healthy postmenopausal women without a previous history of fracture. In the in vitro dissolution test, alendronate was not released from Maxmarvil(®) in pH 1.2 phosphate buffer solution but released in pH 6.0 and 6.8 phosphate buffer solutions and completely dissolved in 30 min. After oral administration of Maxmarvil(®), three out of 18 (16.7 %) women showed mild adverse effects; two myalgia and one upper gastrointestinal discomfort without heartburn. Most of these complaints disappeared during the study without additional treatment. The peak (U max) and the average (U ave) urinary excretion rate of alendronate and the time to reach U max (T max) were 2.94 μg/h, 0.901 μg/h and 6.77 h, respectively. The total cumulative urinary excretion of alendronate (Ae0-24 h) was 21.6 μg (0.432 % of oral alendornate), which was similar to the reported values. Taken together, enteric-coated Maxmarvil(®) is less harmful for the esophagus and gastrointestinal mucosa, shows the same pharmacokinetic profile to conventional alendronate (70 mg) and improves the tolerability of medication in clinical practice.
Archives of Pharmacal Research 05/2013; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: Visfatin is an adipocytokine predominantly expressed in visceral adipose tissue. We examined the relationship between plasma visfatin concentrations and anthropometric and metabolic parameters in children and adolescents, who are relatively less influenced by the effects of accompanying disease. Methods: We studied 135 children and adolescents (8-16 years old). Plasma glucose, insulin, lipid profile, visfatin and other adipocytokine levels were measured. CT scans were performed to evaluate the distribution of abdominal fat. We analyzed the relationship between circulating visfatin levels and anthropometric and metabolic parameters according to central adiposity (total abdominal fat by CT scan). Results: In the lower-adiposity group, plasma visfatin concentrations were significantly correlated with total abdominal fat, visceral fat, subcutaneous abdominal fat, plasma triglyceride level and homeostasis model assessment of insulin resistance (HOMA-IR). In a multiple linear regression analysis, visceral fat and triglycerides were independently associated with plasma visfatin levels. In the higher-adiposity group, plasma visfatin concentrations were not correlated with visceral fat or HOMA-IR but were significantly correlated with circulating interleukin-6 levels. Conclusion: These data suggest that the relationship between plasma visfatin concentrations and metabolic parameters differs according to central adiposity and that plasma visfatin concentrations are correlated with visceral fat and triglyceride levels, especially in children and adolescents with lower adiposity.
Hormone Research in Paediatrics 04/2013; · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An engineered Escherichia coli strain that produces 1-propanol under aerobic condition was developed based on an L-threonine-overproducing E. coli strain. First, a feedback resistant ilvA gene encoding threonine dehydratase was introduced and the competing metabolic pathway genes were deleted. Further engineering was performed by overexpressing the cimA gene encoding citramalate synthase and the ackA gene encoding acetate kinase A/propionate kinase II, introducing a modified adhE gene encoding an aerobically functional AdhE, and by deleting the rpoS gene encoding the stationary phase sigma factor. Fed-batch culture of the final engineered strain harboring pBRthrABC-tac-cimA-tac-ackA and pTacDA-tac-adhE(mut) allowed production of 10.8 g L(-1) of 1-propanol with the yield and productivity of 0.107 g g(-1) and 0.144 g L(-1) h(-1), respectively, from 100 g L(-1) of glucose, and 10.3 g L(-1) of 1-propanol with the yield and productivity of 0.259 g g(-1) and 0.083 g L(-1) h(-1), respectively, from 40 g L(-1) glycerol.
[Show abstract][Hide abstract] ABSTRACT: Platform chemicals composed of 2-6 carbons derived from fossil resources are used as important precursors for making a variety of chemicals and materials, including solvents, fuels, polymers, pharmaceuticals, perfumes, and foods. Due to concerns regarding our environment and the limited nature of fossil resources, however, increasing interest has focused on the development of sustainable technologies for producing these platform chemicals from renewable resources. The techniques and strategies for developing microbial strains for chemicals production have advanced rapidly, and it is becoming feasible to develop microbes for producing additional types of chemicals, including non-natural molecules. In this study, we review the current status of the bio-based production of major C2-C6 platform chemicals, focusing on the microbial production of platform chemicals that have been used for the production of chemical intermediates, building block compounds, and polymers.
Biotechnology and Bioengineering 07/2012; 109(10):2437-59. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For the prevention of osteoporotic fracture, adequate screening and treatment are important. However, there are few published data on diagnosis and treatment rates of osteoporosis in Asia. We used data from the fourth Korea National Health and Nutrition Examination Survey 2008-2009 to estimate the nationwide prevalence, physician diagnosis rate, and treatment rate of osteoporosis in adults aged 50 years and older. The bone mineral density (BMD) measurements of central skeletal sites (lumbar spine, femoral neck, and total hip) were obtained using dual-energy X-ray absorptiometry (DXA) (Discovery-W; Hologic Inc., Waltham, MA, USA). Diagnosis of osteopenia or osteoporosis was defined by the World Health Organization (WHO) T-score criteria. The prevalence of osteoporosis in adults aged 50 years or older was 35.5% in women and 7.5% in men. The prevalence of osteoporosis in Korea was similar to other East Asian countries but higher than that in Caucasians. Lumbar spine bone density T-scores tended to be lower than those of the femoral neck or hip. The estimated diagnosis rate was 26.2% (women 29.9%, men 5.8%) and the treatment rate was 12.8% (women 14.4%, men 4.0%). The physician diagnosis rate was significantly higher in females aged 66 to 68 years who were the beneficiaries of the national screening program than that in females of other ages (43.6% versus 28.1%, p < 0.05). The national screening program for osteoporosis may have contributed to an increased diagnosis rate in older Korean women. However, it was evident that treatment following a diagnosis of osteoporosis was still inadequate.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2012; 27(9):1879-86. · 6.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sarcopenia is an important factor of functional impairment related to aging. This study is conducted to investigate the prevalence of sarcopenia and sarcopenic obesity in Korean population.
Representative Korean men (4,486) and women (5,999) aged 20 years or older were analyzed from the Fourth Korean National Health and Nutritional Examination Surveys. Sarcopenia was classified into Class I defined relative skeletal muscle mass loss within 1-2 SD of the gender-specific mean for healthy young adults and Class II below 2 SD. Relative skeletal muscle mass was represented by the appendicular skeletal muscle mass adjusted by height and body weight. Sarcopenic obesity was considered present in Class II sarcopenic participants whose waist circumference was more than or equal to 90 cm for men and more than or equal to 85 cm for women, respectively.
The prevalence of Class II sarcopenia in the Korean elderly population was 12.4% for men and 0.1% for women by height-adjusted definition and 9.7% for men and 11.8% for women by weight-adjusted definition. The prevalence of sarcopenic obesity was 7.6% for men and 9.1% for women by weight-adjusted definition but nearly zero for men and women by height-adjusted definition. The prevalence of sarcopenia increased with age for men but for women only when applied with weight-adjusted definition.
The prevalence of sarcopenia and sarcopenic obesity differs by gender and definition criteria. The height-adjusted definition may tend to underestimate the prevalence of sarcopenia and sarcopenic obesity, especially in women.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2012; 67(10):1107-13. · 4.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes is a major health problem in Korea. However, interest in the quality of life in patients with diabetes is low. We examined the effects of diabetes on health-related quality of life (HRQoL) and compared it with HRQoL in the general Korean population using the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009).
Using KNHANES IV data, we compared EuroQol (EQ)-5D and EQ-visual analogue scale (VAS) scores after adjusting for sociodemographic and psychosocial factors as well as for comorbidities (hypertension, heart disease, stroke, arthritis, and chronic renal disease). Logistic regressions were used to explore determinants for the lowest quintile HRQoL scales in the diabetes group.
The mean age of the 14,441 enrolled subjects (6,129 men and 8,312 women) was 52.5±14.5 years. The mean EQ-5D and EQ-VAS scores were significantly lower in the diabetes group (EQ-5D. 0.87; EQ-VAS, 71.94) than in the non-diabetes group (EQ-5D, 0.94; EQ-VAS, 77.40) (P<0.001). Self-reported depressive symptom had a significant effect on lowering the EQ-VAS (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1 to 2.6) in the diabetes group. Stress level had a significant effect in lowering both the EQ-5D (OR, 2.0; 95% CI, 1.3 to 2.9) and the EQ-VAS (OR, 1.9; 95% CI, 1.3 to 2.9). HbA1c, diabetes duration, and treatment modalities had no significant effect on lowering HRQoL.
Diabetes was clearly associated with impaired HRQoL compared with the non-diabetic population regardless of comorbidities. Therapeutic approaches should focus much more on the subjective perception of health in patients with diabetes.
[Show abstract][Hide abstract] ABSTRACT: The increasing oil price and environmental concerns caused by the use of fossil fuel have renewed our interest in utilizing biomass as a sustainable resource for the production of biofuel. It is however essential to develop high performance microbes that are capable of producing biofuels with very high efficiency in order to compete with the fossil fuel. Recently, the strategies for developing microbial strains by systems metabolic engineering, which can be considered as metabolic engineering integrated with systems biology and synthetic biology, have been developed. Systems metabolic engineering allows successful development of microbes that are capable of producing several different biofuels including bioethanol, biobutanol, alkane, and biodiesel, and even hydrogen. In this review, the approaches employed to develop efficient biofuel producers by metabolic engineering and systems metabolic engineering approaches are reviewed with relevant example cases. It is expected that systems metabolic engineering will be employed as an essential strategy for the development of microbial strains for industrial applications.
[Show abstract][Hide abstract] ABSTRACT: Free fatty acids (FFAs) lead to the activation of inflammatory pathways related to the induction of insulin resistance. Visfatin is known to play a role in obesity-related metabolic diseases and inflammatory conditions. Here, the role of visfatin in FFA-induced inflammation was investigated in hepatocytes. The following factors were examined: (1) the protein and messenger RNA (mRNA) expression of visfatin in the liver tissue of insulin-resistant rats and in (2) in HepG2 cells treated with palmitate, (3) the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α in HepG2 cells transfected with visfatin-specific small interfering RNA, and (4) the expression of visfatin in HepG2 cells treated with a nuclear factor-κB (NF-κB) inhibitor (SN50) and infected with Ad-IκBα. The protein and mRNA levels of visfatin were significantly higher in insulin-resistant rat liver tissue compared with the control group. Visfatin expression and protein synthesis significantly increased in HepG2 cells treated with palmitate in a time- and concentration-dependent manner. Visfatin-specific small interfering RNA significantly decreased the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α. A NF-κB inhibitor induced the downregulation of visfatin in HepG2 cells following treatment with palmitate. HepG2 cells infected with Ad-IκBα showed decreased expression of visfatin following treatment with palmitate. The expression of visfatin is closely associated with the expression of proinflammatory cytokines in FFA-induced inflammation and is significantly decreased by NF-κB inhibition in HepG2 cells. Visfatin may play a role in FFA-induced inflammation in hepatocytes through the NF-κB pathway.
Metabolism: clinical and experimental 06/2011; 60(12):1781-9. · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: From a young age, males are at higher cardiovascular risk than females. Dyslipidemia, including a higher burden related to small low-density lipoproteins (LDL), plays an important role in precipitating atherosclerosis in both males and females. We investigated sex differences in atherogenic lipoprotein burden and the independent predictors of LDL particle size in children and adolescents. We measured the concentrations of total testosterone, sex hormone-binding globulin, estradiol, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and LDL particle size in 135 children and adolescents (67 boys, 68 girls). The free androgen index was significantly and negatively correlated with LDL particle size (r = -0.273, P = 0.026) in boys, but estrogen and LDL particle size were not related. In a stepwise multiple regression analysis adjusted for body mass index, age, and homeostasis model assessment for insulin resistance, free androgen index was still an independent predictor of LDL particle size in boys (R(2) = 0.075, P = 0.026). The prominent decrease in LDL particle size along with increased testosterone concentrations in males might explain why they are more likely to display atherogenic dyslipidemia from adolescence.
Journal of Korean medical science 04/2011; 26(4):534-9. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptors (TLRs) are germline-encoded innate immune receptors that recognize invading micro-organisms and induce immune and inflammatory responses. Deregulation of TLRs is known to be closely linked to various immune disorders and inflammatory diseases. Cells at sites of inflammation are exposed to hypoxic stress, which further aggravates inflammatory processes. We have examined if hypoxic stress modulates the TLR activity of macrophages. Hypoxia and CoCl(2) (a hypoxia mimetic) enhanced the expression of TLR4 messenger RNA and protein in macrophages (RAW264.7 cells), whereas the messenger RNA of other TLRs was not increased. To determine the underlying mechanism, we investigated the role of hypoxia-inducible factor 1 (HIF-1) in the regulation of TLR4 expression. Knockdown of HIF-1alpha expression by small interfering RNA inhibited hypoxia-induced and CoCl(2)-induced TLR4 expression in macrophages, while over-expression of HIF-1alpha potentiated TLR4 expression. Chromatin immunoprecipitation assays revealed that HIF-1alpha binds to the TLR4 promoter region under hypoxic conditions. In addition, deletion or mutation of a putative HIF-1-binding motif in the TLR4 promoter greatly attenuated HIF-1alpha-induced TLR4 promoter reporter expression. Up-regulation of TLR4 expression by hypoxic stress enhanced the response of macrophages to lipopolysaccharide, resulting in increased expression of cyclooxygenase-2, interleukin-6, regulated on activation normal T cell expressed and secreted, and interferon-inducible protein-10. These results demonstrate that TLR4 expression in macrophages is up-regulated via HIF-1 in response to hypoxic stress, suggesting that hypoxic stress at sites of inflammation enhances susceptibility to subsequent infection and inflammatory signals by up-regulating TLR4.