Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats

Purpose

Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator-activated receptor (PPAR)-γ has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-α, PPAR-γ, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-α are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats.

Materials and Methods

Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α in lung tissues were measured using real time PCR.

Results

PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-γ expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-γ expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-α expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-α, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats.

Conclusion

PPAR-γ was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.     

Serum IL-6 Level May Have Role in the Pathophysiology of Unexplained Infertility

Problem  The aim of this study was to compare the serum levels of interleukin (IL)-6 of women with unexplained infertility with fertile subjects.
Method of study  Serum IL-6, and tumor necrosis factor-α (TNF-α) levels of 45 infertile and 44 fertile women on day 3 of menstrual cycle were assessed and compared for this prospective controlled study.
Results  The mean serum IL-6 level was significantly higher in women with unexplained infertility, compared with fertile women (5.71 ± 1.81 and 4.31 ± 1.79, P  < 0.001, Student's t -test). There was no significant difference in TNF-α level among the groups.
Conclusion  Significant difference in serum IL-6 levels between unexplained infertile and fertile women suggests that this cytokine may be involved in pathophysiology of unexplained infertility.     

Inflammatory Pathways in Liver Homeostasis and Liver Injury

The liver is a unique organ with respect to its anatomical location, allowing continuous blood flow from the gastrointestinal tract through the sinusoids, and its cellular composition, comprising metabolically active hepatocytes, nonhepatocytic parenchymal cells, and various immune cell populations. Cytokines are key mediators within the complex interplay of intrahepatic immune cells and hepatocytes, as they can activate effector functions of immune cells, as well as hepatocytic intracellular signaling pathways controlling cellular homeostasis. Kupffer cells and liver-infiltrating monocyte-derived macrophages are primary sources of cytokines such as tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6. The liver is also enriched in natural killer (NK) and NK T cells, which fulfill functions in pathogen defense, T cell recruitment, and modulation of liver injury. TNF-alpha can activate specific intracellular pathways in hepatocytes that influence cell fate in different manners, e.g., proapoptotic signals via the caspase cascade, but also survival pathways, namely the nuclear factor (NF)-kappaB pathway. NF-kappaB regulates important functions in liver physiology and pathology. Recent experiments with genetically modified mice demonstrated important and partly controversial functions of this pathway, e.g., in cytokine-mediated hepatocyte apoptosis or ischemia–reperfusion injury. The exact dissection of the contribution of recruited and resident immune cells, their soluble cytokine and chemokine mediators, and the intracellular hepatocytic response in liver homeostasis and injury could potentially identify novel targets for the treatment of acute and chronic liver disease, liver fibrosis, or cirrhosis.     

Granulomatous disease in common variable immunodeficiency

Granulomatous disease occurs in 8–22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2–59). 14 had granulomas 1–18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues.     

Consumption of star fruit juice on pro-inflammatory markers and walking distance in the community dwelling elderly

PurposeThis study aimed to evaluate the effect of star fruit juice supplementation on tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23) and interleukin-2 (IL-2), nitric oxide (NO), and 6 min walking distance (6MWD) in a group of elderly individuals.MethodsTwenty-nine individuals (20 males, 9 females) with a mean age of 72.4 ± 8.3 years completed this study. A two-week control period was followed by four weeks of 100 g fresh star fruit juice consumption twice per day after meals.ResultsPlasma TNF-α, IL-23, IL-2, NO and the 6MWD were evaluated twice during the control period (weeks 0 and 2) and once after the star fruit juice consumption (week 6).ResultsThe results showed that all parameters in the blood did not change significantly during the control period. After 4 weeks of star fruit juice consumption, a significant reduction in NO, TNF-α and IL-23 was found; however, there was no change in IL-2. Moreover, the 6MWD increased significantly at week 6, when compared to that at week 0 and 2. Furthermore, the results also showed a significantly positive and negative correlation of NO and TNF-α to the 6MWD, but no correlation of IL-23 and IL-2.ConclusionThis preliminary study concluded that consumption of star fruit juice at 100 g twice daily for one month can significantly depress the pro-inflammation cytokines: TNF-α, IL-23, and NO, while increasing walking distance. Low TNF-α and high NO also present a significant correlation to walking capacity in elderly individuals.     

Circulating levels of interleukin-17A,tumor necrosis factor-alpha,interleukin-18, interleukin-10, and cognitive performance of patients with relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40–70%) of cognitive impairment.

The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS).

Methods

The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA).     

Behçet's syndrome: New insights into pathogenesis and management

Behçet's syndrome (BS) is a multisystem vasculitis with an unknown etiology and an unique geographic distribution. The pathogenesis of BS is complex and currently not fully understood. Since the 1970's there have been different attempts to classify BS within the specific group of diseases such as spondyloarthritis, autoimmune and more recently autoinflammatory disease. However current evidence suggests that BS does not easily fit into any one of these diseases and we propose the possibility that the construct we take as BS might represent more than one disease.The management of BS usually depends on clinical presentation and organ involvement. Traditional immunosuppressives and concomitant use of corticosteroids have been the main therapeutic choice for many years. There is growing experience with biologic therapeutics especially with tumor necrosis factor-alpha (TNF-alpha) antagonists in the management of refractory eye, gastrointestinal and neurologic involvement in BS.In this review we have proposed a different perspective about the disease mechanisms of BS and have summarized the current management strategies in BS in the light of available evidence.     

Tumor necrosis factor-alpha release from rat pulmonary leukocytes exposed to ultrafine cobalt:in vivo andin vitro studies

Ultrafine cobalt (Uf-Co), one of the new category of ultrafine particles, is generated in some industrial situations and it also exists in environmental particles. The aim of this study was to investigate the ability of rat pulmonary leukocytes to release tumor necrosis factor alpha (TNF-alpha) after exposure to Uf-Coin vivo andin vitro. Rats were intratracheally instilled with 1 mg of Uf-Co, and then wet lung weight and bronchoalveolar lavage fluid (BALF) profile were analysed 1, 3, 7, 15, and 30 days later. The effects of Uf-Co on indices that can be presumed to reflect epithelial injury and permeability (lactate dehydrogenase (LDH) and total protein (TP)) were increased throughout the 30 day post-exposure period. Furthermore, at 3 days after exposure, leukocytes were collected by bronchoalveolar lavage (BAL). After 3, 6, 12, 24, 48, and 72 hours of incubation, TNF-alpha in supernatants were determined by ELISA method. The results showed that TNF-alpha secretion by activated leukocytes from rats instilled with Uf-Co was significantly higher than that of the controls. BAL leukocytes from the lung of exposed rats revealed time-arid dose-related increases in TNF-alpha release. In conclusion, our results reveal, for the first time to our knowledge, that exposure to Uf-Co can stimulate leukocytes to secrete TNF-alpha. These data suggest that the TNF- alpha release from pulmonary leukocytes probably plays a role in the pathogenesis of “cobalt lung”.     

Microtubule stabilization opposes the (TNF-α)-induced loss in the barrier integrity of corneal endothelium

Microtubule disassembly breaks down the barrier integrity in a number of epithelial and endothelial monolayers. This study has investigated effects of TNF-α, which is implicated in corneal allograft rejection, on microtubules and barrier integrity in cultured bovine corneal endothelial cells. Exposure to TNF-α led to disassembly of the microtubules, and also caused disruption of the perijunctional actomyosin ring (PAMR). As a measure of barrier integrity, trans-endothelial electrical resistance (TER) was determined based on electrical cell-substrate impedance sensing in realtime. Exposure to TNF-α caused a slow decline in TER for > 20 h, and a similar exposure to cells grown on porous culture inserts led to a significant increase in permeability to FITC dextran. These changes, indicating a loss of barrier integrity, were also reflected by dislocation of ZO-1 at the cell border and disassembly of cadherins. These effects of TNF-α were inhibited upon stabilization of microtubules by pre-treatment with paclitaxel or epothilone B. Microtubule stabilization may be a useful strategy to overcome (TNF-α)-induced loss of the barrier integrity of corneal endothelium during inflammation associated with transplant rejection and uveitis.