Increased Mucus Secretion Research Articles

The therapeutic effect of Drynariae Rhizoma in a mouse model of allergic asthma

Objective : Allergic asthma is a chronic airway disease that affects millions of people in the developed world. The disease is characterized by concurring airway inflammation, Th2 cytokine production, increased mucus secretion, airway hyperresponsiveness (AHR) to inhaled antigen, and pulmonary fibrosis. To investigate the therapeutic and anti-asthmatic effects of Drynariae Rhizoma (DR), we examined the influence of DR on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods : In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of DR on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA specific IgE production in a mouse model of asthma. Results : In asthmatic mice, we found that DR.treated groups had suppressed eosinophil infiltration, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13 and OVA specific IgE. Conclusions : Our data suggest that the therapeutic mechanism by which DR effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production and eosinophil infiltration.

Translocation of infectious pancreatic necrosis virus across the intestinal epithelium of Atlantic salmon ( Salmo salar L.)

Infectious pancreatic necrosis virus (IPNV) is a viral disease that afflicts salmon aquaculture worldwide. Transmission of viral diseases may occur via the skin, gills or intestine but the main entry route for IPNV is not known. However, acute inflammation of the intestinal mucosa is an early symptom in infected fish which suggests transmission through an oral route. The main aim of this study is to determine if IPNV can translocate across the intestinal epithelium. It also aims to investigate how acute and chronic IPNV exposure as well as stress affects the physiological barrier functions of the intestinal epithelium. Possible translocation of IPNV across the intestinal mucosa as well as effects of virus on intestinal barrier function was measured in vitro, using the Ussing chamber technique. IPNV was translocated across both proximal and distal segments of the intestine with a higher rate in distal compared to proximal intestine. The translocated virions caused cytopathic effects on cultured Chinook salmon embryo cells (CHSE-214), proving viability and high virulence. Intestinal barrier function was disturbed as assessed by increased permeability for 14C-mannitol in the proximal region after exposure to IPNV in vitro. The same pattern was observed after prolonged exposure to IPNV in vivo. Further, the intestine appeared to respond with an increased mucus secretion, as indicated through increased TER after prolonged IPNV exposure. No additional effects of cortisol implantation on barrier function were observed. In conclusion, this study demonstrates that both proximal and distal intestine can be used by IPNV as a route of infection and that the intestinal barrier function is negatively affected by exposure to IPNV.

Longevity in Mice Is Promoted by Probiotic-Induced Suppression of Colonic Senescence Dependent on Upregulation of Gut Bacterial Polyamine Production

BackgroundChronic low-grade inflammation is recognized as an important factor contributing to senescence and age-related diseases. In mammals, levels of polyamines (PAs) decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. Reductions in intestinal luminal PAs levels have been associated with intestinal barrier dysfunction. The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations.Methodology/Principal FindingsWe supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared using Kaplan–Meier survival curves. LKM512-treated mice survived significantly longer than controls (P<0.001); moreover, skin ulcers and tumors were more common in the control mice. We then analyzed inflammatory and intestinal conditions by measuring several markers using HPLC, ELISA, reverse transcription-quantitative PCR, and histological slices. LKM512 mice showed altered 16S rRNA gene expression of several predominant intestinal bacterial groups. The fecal concentrations of PAs, but not of short-chain fatty acids, were significantly higher in LKM512-treated mice (P<0.05). Colonic mucosal function was also better in LKM512 mice, with increased mucus secretion and better maintenance of tight junctions. Changes in gene expression levels were evaluated using the NimbleGen mouse DNA microarray. LKM512 administration also downregulated the expression of ageing-associated and inflammation-associated genes and gene expression levels in 21-month-old LKM512-treated mice resembled those in 10-month-old untreated (younger) mice.Conclusion/SignificanceOur study demonstrated increased longevity in mice following probiotic treatment with LKM512, possibly due to the suppression of chronic low-grade inflammation in the colon induced by higher PA levels. This indicates that ingestion of specific probiotics may be an easy approach for improving intestinal health and increasing lifespan. Further studies are required to clarify its effectiveness in humans.

Isolate two Crustaceans which infect Cyprinus carpio L. from Bab Al-Muatham fish markets, Baghdad City

During the period from November 2007 till October 2008, a total of 255 specimens of the cyprinid fish, from freshwater fish Cyprinus carpio Linnaeus, 1758, were collected from fish markets east of Baghdad city. Microscopic examination of these fishes revealed that they were infected with two species of the crustaceans ]Argulus foliaceus (0.8%) and Ergasilus sieboldi (20%)[.The present study included the following: The clinical signs which were caused by the crustaceans, which included redness and an opacity of the skin, increase of mucus secretion and rapid movements of the operculum. The percentage incidence of the infection with these parasites were also found to be related to different length groups of the host, the larger fishes were more infected (95.2%) while the smaller fishes were less infected (0.8%).

The Role of Cytokines in Atopic Asthma

Atopic asthma results from airway inflammation triggered by an environmental allergen. Symptoms include wheezing, dyspnea and cough, airway narrowing and/or hyperresponsiveness to several inhaled stimuli. Inflammation develops in a two-phase fashion. The first phase after exposure to the allergen consists of degranulation and release of both histamine and other stored preformed inflammatory mediators as well as newly synthesized ones, including cytokines, all of which increase mucus secretion and smooth muscle contraction. The second phase occurs later and lasts longer; it is due to different molecules: several cytokines and chemokines, arachidonic acid derivatives, enzymes such as metalloproteinases and cell adhesion molecules. Cytokines are key players in the chronic inflammation in asthma patients, but details on their role and interactions still remain undetermined. Recent evidence suggests that allergic asthma is a multifaceted condition actively controlled by effector as well as regulatory T cells (Tregs). T helper (Th) 2 cells and Th17 cells increase airway inflammation, while Tregs are anti- inflammatory. Cytokines are involved in the development and activation of all T cell subpopulations. They are also involved directly or indirectly in most approaches to asthma treatment. Several cytokines have been tested as therapeutic targets and some of the currently used therapies like corticosteroids, beta agonists and allergen immunotherapy affect cytokine production. The increased knowledge on cytokine interplay and lymphocyte subsets should generate new therapeutic strategies in the near future.

Application of proteomics in asthma research

Bronchial asthma is caused by allergic airway inflammation, resulting in reversible airway obstruction, characterized by airway hyper-responsiveness, bronchoconstriction, increased mucus secretion and an increase in lung vessel permeability. The pathophysiological changes in asthma have been attributed to the altered expression of biologically plausible proteins associated with transcriptional pathways, inflammatory mediators, chemokines, cytokines, apoptosis and cell proliferation. Such multifactorial diseases characteristically involve an interplay of many genetic variations of molecular and biochemical pathways and their interactions with environmental factors. The complex nature of the asthma phenotype, together with genetic heterogeneity and environmental influences, has made it difficult to uncover the aspects that underlie this common disease. Recently, genomic and proteomic technologies have been developed to identify associations between genes, proteins and disease. This approach, called ‘omics biology’, aims to recognize early onset of disease, institute preventive treatment and identify new molecular targets for novel drugs in multifactorial diseases. This article reviews examples of how proteomic technology can be used to find asthma marker proteins (from the cell model to clinical samples). Identification of protein changes in different stages of asthma could provide further insights into the complex molecular mechanisms involved in this disease. These studies provide new insights for finding novel pathological mediators and biomarkers of asthma.

Effects of fudosteine, a new mucoactive drug, on the increase in mucus secretion produced by secretagogues in human pulmonary mucoepidermoid carcinoma cells

The purpose of this study was to clarify the effects of fudosteine ((—)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid), a new mucoactive drug, on mucus secretion in the human pulmonary mucoepidermoid carcinoma cell line NCI-H292. NCI-H292 cells produced hyaluronidase-resistant high-molecular-weight glycoconjugates (HMWG), which were eluted in the void volume on Superose 6HR column chromatography. ATP, bradykinin, and methacholine increased the basal secretion of [14C]glucosamine-labelled HMWG in NCI-H292 cells. Fudosteine significantly suppressed the HMWG secretion induced by ATP or bradykinin, but not that induced by methacholine. Other mucoactive drugs, such as ethylcysteine, ambroxol and carboxymethylcysteine, did not affect the increase in HMWG. These results indicate that fudosteine suppresses the mucin secretion induced by ATP and bradykinin in airway mucus-producing cancer cells.

Histopathological and biochemical alterations of the earthworm ( Lumbricus Terrestris) as biomarker of soil pollution along Porsuk River Basin (Turkey)

This study investigated biomarker responses of the earthworm Lumbricus terrestris in order to evaluate the soil pollution along Porsuk River Basin. Samples consisted of animals from six sites that are agricultural regions and a forested control. Histopathological and biochemical alterations were examined. Significant histopathological alterations were observed in animals from three of the sampling sites. There was an enlargement of epithelial cell lining, mucus cell hyperplasia and increase in mucus secretion. Circular and longitudinal muscles lost their structural integrity. Chloragogenous tissue was dilated and vocuolized. Necrosis was observed in the cells and tissues of some affected worms. A load of heavy metals in tissues of animals was determined. Heavy metals were found to be accumulated particularly in longitudinal muscles of animals. CAT activity was found to be increased in animals from three of the experimental sites. GST activity was also increased in five sites while it was stable in one site. The results have shown that animals from locations particularly that are close to urbanized and industrialized regions were seriously affected from the soil pollution around the basin. These results are reflecting the biological effects of soil pollution around Porsuk River Basin on the indicator organism L. terrestris and constitute an early warning of ecological change in relation to human health.

Protective effect of rhubarb on the intestinal mucosal barrier.

To investigate the mechanism of rhubarb protection of the gut barrier. The gut barrier damage models caused by hemorrhagic shock and intraperitoneal endotoxin were used to study the protective effect of rhubarb on the intestinal mucosal barrier. Rats were randomly divided into four groups, as follows: treatment (rhubarb) group; Positive control group; Negative control group; Placebo treatment group. Plasma endotoxin, tissue superoxidedismutase (SOD) and lipoperoxide (LPO) concentrations were measured and histological analysis was performed. Rhubarb was observed to have a protective effect on the gut. Rhubarb decreased intestinal permeability, attenuated endotoxin absorption (endotoxin serum levels: shock group 0.557 EU/mL ± 0.069 EU/mL vs rhubarb group 0.345 EU/mL ± 0.055 EU/mL), and decreased tissue SOD and tissue LPO levels (SOD serum, intestine and liver levels: endotoxin group 122.92 NU/mL ± 43.19 NU/mL, 292.24 NU/mL ± 88.76 NU/mL, 272.70 NU/mL ± 85.79 NU/mL vs rhubarb group 312.23 NU/mL ± 54.93 NU/mL, 391.09 NU/mg ± 98.16 NU/mg, 542.86 NU/mg ± 119.93 NU/mg; LPO content in the intestine and liver: endotoxin group 8.57 μmol/L ± 2.58 μmol/L, 86.97 μmol/L ± 46.54 μmol/L vs rhubarb group 3.05 μmol/L ± 1.13 μmol/L, 13.18 μmol/L ± 19.64 μmol/L). Gut histopathology revealed that rhubarb promoted goblet cell proliferation, increased mucus secretion and protected intestinal mucosa in the hemorrhagic shock model. Rhubarb may protect the gut barrier by decreasing intestinal permeability, scavenging oxygen free radicals, and promoting goblet cell proliferation within the intestinal mucosa.

JNK activation is responsible for mucus overproduction in smoke inhalation injury

BackgroundIncreased mucus secretion is one of the important characteristics of the response to smoke inhalation injuries. We hypothesized that gel-forming mucins may contribute to the increased mucus production in a smoke inhalation injury. We investigated the role of c-Jun N-terminal kinase (JNK) in modulating smoke-induced mucus secretion.MethodsWe intubated mice and exposed them to smoke from burning cotton for 15 min. Their lungs were then isolated 4 and 24 h after inhalation injury. Three groups of mice were subjected to the smoke inhalation injury: (1) wild-type (WT) mice, (2) mice lacking JNK1 (JNK1-/- mice), and (3) WT mice administered a JNK inhibitor. The JNK inhibitor (SP-600125) was injected into the mice 1 h after injury.ResultsSmoke exposure caused an increase in the production of mucus in the airway epithelium of the mice along with an increase in MUC5AC gene and protein expression, while the expression of MUC5B was not increased compared with control. We found increased MUC5AC protein expression in the airway epithelium of the WT mice groups both 4 and 24 h after smoke inhalation injury. However, overproduction of mucus and increased MUC5AC protein expression induced by smoke inhalation was suppressed in the JNK inhibitor-treated mice and the JNK1 knockout mice. Smoke exposure did not alter the expression of MUC1 and MUC4 proteins in all 3 groups compared with control.ConclusionAn increase in epithelial MUC5AC protein expression is associated with the overproduction of mucus in smoke inhalation injury, and that its expression is related on JNK1 signaling.

Detection of koi herpesvirus (KHV) from koi (Cyprinus carpio koi) broodstock in South Korea

The presence of koi herpesvirus (KHV) was confirmed in three ornamental koi broodstocks for breeding purposes. The broodstocks showed poor appetite, lethargy, abnormal swimming behavior with gasping movements in shallow water and increased mucus secretion. Histopathologically, the gill showed diffuse necrosis of the branchial epithelial cells and diffuse lymphocytic–monocytic interstitial nephritis with necrosis of the tubular epithelial cells predominantly found in these three broodstocks. The presence of viral intranuclear inclusion bodies were also observed. KHV was not isolated using KF-1 cell line but PCR positive results at 484bp DNA product was confirmed in all organs of the fish and quatification of KHV genomic DNA using real-time Taqman PCR in all organs ranged from 1.32×10−9 to 1.39×10−9 copy numbers. The analysis of sequencing data of 484bp fragments of KHV DNA of three Korean isolates revealed 100% identities with each other and closely related (98 to 99%) to the known CyHV-3 type of KHV. This report confirmed the presence of KHV infection in one koi commercial farm in South Korea using pathological and molecular methods.

Assessment of acquired protection levels against the parasite Neobenedenia girellae (Monogenea) between body surface sites including fins of amberjack Seriola dumerili (Carangidae) and the skin in response to the parasite infection

This study investigated acquired protection against the parasite Neobenedenia girellae (Capsalidae) at multiple body surface sites and fins of the amberjack Seriola dumerili (Carangidae). We also assessed histopathology of skin between naïve and primed fish. Fish, which were previously infected with N. girellae and treated by freshwater bath, was referred to as “primed fish”. The number of N. girella was significantly lower on primed S. dumerili than on naïve fish at 4 days and 8 days after exposure to N. girellae oncomiracidia when they were exposed in the same aquarium. Parasite numbers on pectoral and pelvic fins and on the dorsal (region 2) and belly side of fore body (region 3) were also significantly lower on primed fish than on naïve fish. In addition, the length of parasites was significantly shorter from primed S. dumerili fins than from naïve fish. However, in the head region (region 1), parasite number and length were similar. These results show that acquired protection was high in pectoral and pelvic fins and in regions 2 and 3 but low in region 1. Epidermis from regions 2 and 3 of oncomiracidia-exposed naïve fish at 4 days and 8 days after exposure was significantly thinner than the skin of an uninfected naïve fish, whereas epidermis of oncomiracidia-exposed primed fish at 8 days was significantly thicker than skin of uninfected primed fish. Furthermore, mucus cell numbers in regions 2 and 3 of primed fish was markedly increased at 4 days post-exposure as compared to naïve fish. Taken together, these results suggest that increased numbers of mucus cells and increased mucus secretion in fish skin may have contributed to acquired protection against N. girellae infection.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

BackgroundCystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice.MethodsCftrtm1UNC (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR.ResultsCrypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels.ConclusionsThese results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.

Characterization of leukotrienes in a pilot study of older asthma subjects

Leukotrienes are pro-inflammatory lipid mediators, which are important in asthma leading to its characteristic features of airway bronchoconstriction, wheezing, increased mucus secretion and decreased mucociliary clearance. Aging results in changes in immune function and we have previously demonstrated age-related differences in levels of neutrophil elastase, MMP-9, and IL-8 in asthma subjects. We sought to determine whether leukotriene levels differed between young and older asthmatics.

Surface architecture of the opercular epidermis and epithelium lining the inner surface of the operculum of a walking catfish, Clarias batrachus

In Clarias batrachus, the opercular epidermis (OE) and epithelium lining the inner surface of the operculum (EISO) showed significant differences in their surface architecture, such being correlated with different conditions at the two locations. The surfaces of the epithelial cells had characteristically intricate patterns of microridges, which were mostly short-ridged with narrow spaces between them (OE) or high-ridged and widely spaced (EISO). These patterns were believed to be associated with the relative extent of surface secretory vesicles, present for the secretion and renewal of the extracellular cuticular coat at these locations. Extensively distributed on the OE, wide mucous cell openings enable increased mucus secretion, considered to be an adaptation resulting from the greater need for lubrication, protection and inhibition of invasion and proliferation of pathogenic microorganisms, than at the EISO, where mucous cell apertures were few and narrow. Taste buds were generally situated at papillate, epidermal elevations that projected from the OE surface. This possibly enhances gustatory function, being an adaptation compensating for reduced vision. The absence of taste buds in the EISO suggested that a gustatory function does not occur in that region.

Anti-inflammatory effects of ethanolic extract from Lagerstroemia indica on airway inflammation in mice

In the present study, we investigated whether the Lagerstroemia indica Linn (LI) extract has an anti-inflammatory effect on lung inflammation in ovalbumin-induced asthmatic mice. The LI extract was obtained from dried and powdered whole plants of LI using 80% ethanol. ELISA was performed to evaluate cytokine concentration. BALB/c mice were used as a mouse model of asthma after asthmatic induction by ovalbumin sensitization and inhalation. We examined the effects of the LI extract on leukocyte infiltration and mucus secretion using cell count and histological stain. The amount of cytokines, such as interleukin (IL)-2, IL-4, IL-5, IL-13, and TNF-α, was increased in Jurkat cells using the extract from house dust mites. Increased cytokine concentrations were inhibited by the LI extract. The LI extract suppressed the increased expression of IL-6 after treatment with mite extract of EoL-1 cells and THP-1 cells. In an in vivo experiment using asthmatic mice, the LI extract significantly inhibited leukocytosis and eosinophilia in bronchoalveolar lavage (BAL) fluid and lung tissue samples. The LI extract inhibited the increase in mucus secretion by goblet cells, blocked the production of reactive oxygen species in BAL fluid cells, and blocked the protein expression of IL-5 in BAL fluid. The concentration of ovalbumin-specific IgE in BAL fluid was weakly inhibited by the LI extract. These results suggest that the LI extract may be used as a valuable agent for treating allergic diseases such as asthma due to its anti-inflammatory property.

Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer

Aim of the study Mouriri pusa, popularly known as “manapuçá” or “jaboticaba do mato”, is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects. Materials and methods The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid. Results In the acute model, treatment with either, TF (25 mg/kg) or FF (50 mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers’ regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed. Conclusions Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety.

Nasal and rectal delivery of insulin with chitosan and N-trimethyl chitosan chloride

The aim of this study was to evaluate the ability of TMC, with different degrees of quaternization, to increase insulin absorption in vivo following nasal and rectal administration in rats. Two batches of TMC with different degrees of quaternization (TMC-L, 12.3% quaternized and TMC-H, 61.2% quaternized) and chitosan hydrochloride were administered intranasally (0.25 and 0.5% w/v) and rectally (0.5% w/v) with insulin (4 IU/kg body weight), at a pH of 4.40 and 7.40, in rats. Blood samples were taken over a period of 2 h for measurement of blood glucose levels and plasma insulin levels. Local toxicity evaluation was done by histological examination of the nasal and rectal epithelia. At pH 4.40 all these polymers were able to increase nasal and rectal insulin absorption, compared to the control groups. However, at a pH of 7.40, only TMC-H was able to increase the nasal and rectal absorption of insulin. These results relate to the insolubility of chitosan hydrochloride at neutral pH values, while the charge density of TMC-L is still too low for any significant interaction at pH 7.40. Histological evaluation of the nasal and rectal eptihelia shows no changes in the morphology of the cells after exposure to these polymers. Only slight congestion of the nasal submucosa was observed and all these polymers led to a mild increase in mucus secretion at pH 4.40. Highly quaternized TMC proves to be a potent absorption enhancer in vivo, especially at neutral pH values where chitosan salts are ineffective.

Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats

We examined the effect of lafutidine, a histamine H(2) receptor antagonist with a mucosal protective action mediated by capsaicin-sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats. Animals were given loxoprofen (10-100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16-dimethyl prostaglandin E(2) (dmPGE(2); 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after. Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE(2) and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN. Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Invariant NKT cells in pig lung: a potential asthma model (141.8)

Abstract Biomedical research in pigs is critical for better human health, as they are immunologically and physiologically more similar to humans, and are an excellent animal model to alleviate human asthma. Natural Killer T (NKT) cells with an invariant TCR are called "invariant NKT" (iNKT). iNKT cells are activated by CD1d-bound glycolipids with a unique α-anomerically linked sugar (e.g. α-GalCer). For the first time in pigs, we detected iNKT cells and CD1d expression. The pig iNKT cells proliferated and secreted both Th1 and Th2 cytokines when cultured in the presence of α-GalCer. In particular, iNKT cells from lung, and lung draining lymph nodes proliferated to higher numbers (&amp;lt;1% to &amp;gt;30%), with the secretion of more cytokines, compared to iNKT cells from other tissues. Recently, “many pivotal roles” played by iNKT cells in asthma pathogenesis have been reported. Direct activation of pig lung iNKT cells using α-GalCer resulted in airway hyperreactivity (AHR), and clinically those pigs had dyspnea with elevated body temperature. The AHR induced pig lung had petechial hemorrhages with increased mucus secretion in the airway. The α-GalCer received pigs had three-fold increase in cytokines, IL-6, IL-12 and IL-10, and two-fold increase in CD1d expression on the dendritic cells and macrophages at post-24 of inoculation. A moderate increase in iNKT cells in lungs of AHR induced pigs was also detected, compared to controls. This work is supported by USDA and NPB grants to RJG.