Maintenance Of Mucosal Integrity Research Articles

Pre and Probiotics to Postbiotics: A Changing Paradigm

The relationship between microbiota and human health has long been stated by Hippocrates said, “Death sits in the bowls” in 400 B.C. With recent scientific advance ments, there is a growing understanding of the significance of microbiota in health and disease. The two-way communication between the host and the microbiota involves the production of various metabolites that play crucial roles in host energy metabolism, influence nervous system function and the gut- brain axis, immune maturation and homeostasis, maintenance of mucosal integrity, treatment of metabolic disorders, anti-obesity, cholesterol lowering, antioxidant, anticancer, antiproliferative and anti-inflammatory properties. Postbiotics are inanimate microorganisms or their compounds, including short-chain fatty acids, exopolysaccharides, vitamins, teichoic acids, bacteriocins, enzymes and peptides that provide health benefits to the host. Postbiotics can be stored under normal environmental conditions, have a prolonged shelf life, easy to transport, and handle and overcome the limitations of probiotic use. As a result, postbiotics have immense potential as a safe and effective means of promoting health and well-being.

Status of salivary human beta defensin-2 in oral potentially malignant disorders and oral cancer: Quest for a novel non-invasive biomarker

Background: Oral cancer ranks sixth among all the types of cancers globally and contributes to significant mortality and morbidity. Inflammation is known to play an important role in tumorigenesis. Human Beta Defensins are a type of AMP that play a role as chemo attractive, antimicrobial, and antitumor agents and also act as immunomodulators. They have also been demonstrated in cancer cell lines. Beta defensins act as tumor suppressor genes by manipulating the tumor microenvironment. The existing literature on human beta defensin-2 activity is scarce. There exists no literature on the comparison of the level of salivary human beta defensin-2 between subjects with oral potentially malignant disorders and oral cancer. Saliva contains constituents that reflect the physiologic state of the body. This can be utilized for rapid and atraumatic diagnosis of diseases owing to its non-invasive nature of collection. Aims and Objectives: The aim of the present study was to assess the level of human beta defensin-2 in the saliva of subjects with oral potentially malignant disorders and oral cancer and compare them with levels in healthy subjects. Materials and methods: The study sample included 75 subjects who were divided into three groups consisting of healthy subjects, subjects with oral potentially premalignant disorders and subjects with oral cancer. Results: The mean salivary Human beta defensin-2 level in subjects with oral cancer was significantly higher than in healthy controls and subjects with oral potentially malignant disorders. The level was highest in the oral cancer group and least in the control group. This difference among the 3 groups was statistically significant. In the group with premalignant disorders, the variation in the level of salivary human beta defensin-2 according to the type of lesion was not statistically significant. Conclusion: This study highlights the diagnostic role of hBD-2 in saliva. The presence of Human beta defensin-2 in the saliva of healthy controls points to its role in the maintenance of mucosal integrity. Elevation in the level of hBD-2 in oral potentially malignant disorders and a further increase in oral cancer indicate the potential use of hBD-2 as a biomarker in early diagnosis of oral cancer. Use of saliva as the diagnostic fluid aids in establishing a non-invasive and atraumatic means of diagnosis.

Assessment of gastroprotective activity of aqueous leaf extract of Ageratum conyzoides L.: Role of mucous cells, anti-apoptotic (Bcl-2) and tumor suppressor (p53) proteins

Introduction: Generally, factors that up-regulate gastric mucosal protective factors or down-regulate aggressive factors contribute to the maintenance of mucosal integrity. This study was done to assess the role of mucous cells, Bcl-2 and p53 proteins during the gastroprotective activity of aqueous extract of Ageratum conyzoides.Methods: The phytochemistry of A. conyzoides extract was analyzed using a gas chromatography-mass spectrometer. Animals were subdivided into five groups, including non-treated normal control group A, non-treated test control group B, and treated groups C-E (Pre-treated with 100, 300, and 500 mg/kg A. conyzoides, respectively for 28 days). After the treatment period, pyloric-ligation was used to induce mucosal injury. Gastric tissues were harvested, grossly examined, and processed for histological, histochemical, and immunohistochemical studies. Stained sections were examined and quantified using image-J software. The data were analyzed using IBM-SPSS (version 23), and comparisons were checked via t test and analysis of variance.Results: Mild mucosal erosion was observed in the treated groups, but intense erosion was prominent in the test control animals. There was an insignificant increase in mucous cells, a significant (P < 0.05) increase in Bcl-2 expression without a significant increase in p53 expression in gastric mucosa of pre-treated animals compared to normal control. Gastric mucosa of test control showed a significant (P < 0.05) decrease in mucous cell count and Bcl-2 expression with a significant concomitant increase in p53 expression.Conclusion: Increased mucous cell population and reciprocal expressions of Bcl-2 and p53 proteins in the gastric mucosa of animals highlighted the sub-cellular mechanisms of gastroprotective activity of A. conyzoides.

PARK7 Diminishes Oxidative Stress-Induced Mucosal Damage in Celiac Disease.

Coeliac disease (CD) is a chronic, immune-mediated small intestinal enteropathy, accompanied with gluten-triggered oxidative damage of duodenal mucosa. Previously, our research group reported an increased mucosal level of the antioxidant protein Parkinson's disease 7 (PARK7) in children with CD. In the present study, we investigated the role of increased PARK7 level on the epithelial cell and mucosal integrity of the small intestine. The presence of PARK7 was investigated using immunofluorescent staining on duodenal mucosa of children with CD and on FHs74Int duodenal epithelial cells. To investigate the role of oxidative stress, FHs74Int cells were treated with H2O2 in the absence or presence of Comp23, a PARK7-binding compound. Intracellular accumulation of reactive oxygen species (ROS) was determined by DCFDA-based assay. Cell viability was measured by MTT, LDH, and Annexin V apoptosis assays. Disruption of cytoskeleton and cell adhesion was investigated by immunofluorescence staining and by real-time RT PCR. Effect of PARK7 on mucosal permeability was investigated ex vivo using intestinal sacs derived from control and Comp-23-pretreated mice. Comp23 treatment reduced the H2O2-induced intracellular accumulation of ROS, thus preserving the integrity of the cytoskeleton and also the viability of the FHs74Int cells. Accordingly, Comp23 treatment increased the expression of antioxidants (NRF2, TRX1, GCLC, HMOX1, NQO1), cell-cycle regulators (TP53, CDKN1A, PCNA, BCL2, BAX), and cell adhesion molecules (ZO1, CDH1, VCL, ITGB5) of H2O2-treated cells. Pretreatment with Comp23 considerably decreased the small intestinal permeability. In this study, we demonstrate that PARK7-binding Comp23 reduces the oxidative damage of duodenal epithelial cells, via increased expression of NRF2- and P53-regulated genes. Our results suggest that PARK7 plays a significant role in the maintenance of mucosal integrity in CD.

Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.

A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.

Eicosanoids in the gastrointestinal tract.

Eicosanoids play important roles in modulating inflammation throughout the body. The gastrointestinal (GI) tract, in part because of its intimate relationship with the gut microbiota, is in a constant state of low-grade inflammation. Eicosanoids like PGs, lipoxins and leukotrienes play essential roles in maintenance of mucosal integrity. On the other hand, in some circumstances, these mediators can become major drivers of inflammatory processes when the lining of the GI tract is breached. Drugs such as nonsteroidal anti-inflammatories, by altering the production of various eicosanoids, can dramatically impact the ability of the GI tract to respond appropriately to injury. Disorders such as inflammatory bowel disease appear to be driven in part by altered production of eicosanoids. Several classes of drugs have been developed that target eicosanoids. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.

Modulation of central endocannabinoid system results in gastric mucosal protection in the rat

Previous findings showed that inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), degrading enzymes of anandamide (2-AEA) and 2-arachidonoylglycerol (2-AG), reduced the nonsteroidal anti-inflammatory drug-induced gastric lesions. The present study aimed to investigate: i./whether central or peripheral mechanism play a major role in the gastroprotective effect of inhibitors of FAAH, MAGL and AEA uptake, ii./which peripheral mechanism(s) may play a role in mucosal protective effect of FAAH, MAGL and uptake inhibitors. Methods: Gastric mucosal damage was induced by acidified ethanol. Gastric motility was measured in anesthetized rats. Catalepsy and the body temperature were also evaluated. Mucosal calcitonin gene-related peptide (CGRP), somatostatin concentrations and superoxide dismutase (SOD) activity were measured. The compounds were injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Results: 1. URB 597, JZL184 (inhibitors of FAAH and MAGL) and AM 404 (inhibitor of AEA uptake) decreased the mucosal lesions significantly given either i.c.v. or i.p. 2. URB 937, the peripherally restricted FAAH inhibitor failed to exert significant action injected i.p. 3. Ethanol-induced decreased levels of mucosal CGRP and somatostatin were reversed by URB 597, JZL 184 and AM 404, the decreased SOD activity was elevated significantly by URB 597 and JZL 184. 4. Neither compounds given i.c.v. influenced gastric motility, elicited catalepsy, or hypothermia. Conclusion: Elevation of central endocannabinoid levels by blocking their degradation or uptake via stimulation of mucosal defensive mechanisms resulted in gastroprotective action against ethanol-induced mucosal injury. These findings might suggest that central endocannabinoid system may play a role in gastric mucosal defense and maintenance of mucosal integrity.

HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication.

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers.

Ulcerative colitis (UC) is associated with a substantial alteration of specific gut commensals, some of which may be involved in microbiota-mediated protection. In this study, microbiota cataloging of UC patients by 16S rRNA microbial profiling revealed a marked reduction of bifidobacteria, in particular the Bifidobacterium bifidum species, thus suggesting that this taxon plays a biological role in the aetiology of UC. We investigated this further through an in vivo trial by testing the effects of oral treatment with B. bifidum PRL2010 in a wild-type murine colitis model. TNBS-treated mice receiving 10(9) cells of B. bifidum PRL2010 showed a marked reduction of all colitis-associated histological indices as well as maintenance of mucosal integrity as it was shown by the increase in the expression of many tight junction-encoding genes. The protective role of B. bifidum PRL2010, as well as its sortase-dependent pili, appears to be established through the induction of an innate immune response of the host. These results highlight the importance of B. bifidum as a microbial biomarker for UC, revealing its role in protection against experimentally induced colitis.

Goblet cell Hypoxia-Inducible Factor (HIF) is necessary for mucin processing and maintenance of mucosal integrity

Abstract Secreted mucus is essential for intestinal homeostasis, separating luminal bacteria from the colonic epithelium and preventing inappropriate inflammation. Perturbations in goblet cell mucus secretion have been shown to lead to spontaneous colitis in mice. Treatment of mice with a prolyl hydroxylase inhibitor (AKB-4924) leads to stabilization of hypoxia inducible factor-1 alpha (HIF-1α) and regulation of hypoxia-responsive genes that promote mucosal protection. Interestingly, goblet cell hyperplasia was observed following in vivo administration of AKB-4924, which may account for the mucosal protection observed. Thus, we hypothesized epithelial stabilization of HIF-1α leads to goblet cell differentiation. Utilizing 3D murine colonic organoid system, treated with a gamma secretase inhibitor (DBZ), AKB-4924 or hypoxia, we analyzed changes in differentiation markers by qPCR. Contrary to our hypothesis, neither AKB-4924 nor hypoxia resulted in the induction of goblet cell differentiation factors. Furthermore, mice lacking HIF-1α in the intestinal epithelium (HIF-1αfl/fl-VillinCRE) exhibited normal colonic goblet cell numbers. However, these goblet cells appeared less organized with diffuse mucin granules. Fluorescent in situ hybridization with a eubacterial probe revealed diminished thickness, with reduced proximity to the microbiome in HIF−/− mice. Finally, profiling the composition of the mucus layer revealed significantly altered expression profile of both secreted and adherent mucins. We conclude that epithelial HIF-1α alters goblet cell function, regulating intestinal mucus, which may contribute to the mucosal-protective role of HIF.

538 Role of the Intestinal Biotin Uptake System (The Sodium-Dependent Multivitamin Transporter, SMVT) in the Maintenance of Mucosal Integrity

538 Role of the Intestinal Biotin Uptake System (The Sodium-Dependent Multivitamin Transporter, SMVT) in the Maintenance of Mucosal Integrity

Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats.

It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored. This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats. Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion. Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach. This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction.

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction.

Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review.

BackgroundHypoxic-ischemic injury is thought to play a significant role in necrotizing enterocolitis (NEC). Nitric Oxide (NO) is the principal inhibitory neurotransmitter in the gut and is involved in regulation of mucosal blood flow and maintenance of mucosal integrity. NO is synthesized from L-arginine by NO synthases. Our primary objective was to determine the effectiveness of supplemental L-arginine versus placebo in prevention of NEC in preterm infants ≤ 34 weeks gestational age by systematic review of published randomized controlled trials (RCTs).MethodsThis review included RCTs in which L-arginine was administered as a supplement to neonates to prevent NEC. Searches were conducted in OVID MEDLINE, EMBASE, PubMed, and CINAHL from their dates of inception to July, 2014. Inclusion criteria were informed parental consent, neonates born at ≤ 34 weeks gestation, and birth weight ≤ 1500 g. Exclusion criteria included neonates with severe congenital anomalies and inborn errors of metabolism. Incidence of NEC was the primary outcome measure. Whole data were analyzed by RevMan 5.1 (Update Software, Oxford, UK). Outcome data were analyzed to determine risk ratios, number needed to treat, confidence intervals, and test for overall effect.ResultsTwo trials including 425 neonates were eligible for this review. Of these, 235 neonates were included in the study. L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02). A similar finding was identified for all stages of NEC (60% reduction, RR 0.40, 95% CI 0.23 to 0.69, NNT = 5) (P = 0.001). At age 3 yrs, there was no significant difference between the 2 groups in terms of any neurodevelopmental disability (RR 0.65; 95% CI 0.23-1.83, P = 0.41).ConclusionsL-arginine supplementation appears to be protective in prevention of NEC in preterm infants and without any significant impact on neurodevelopmental outcomes at 36 months of corrected age. With the addition of the results of one more study to the literature, an intriguing role for L-arginine supplementation continues to gain support. However, large multi-centre RCTs are needed before this can become common practice.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2431-14-226) contains supplementary material, which is available to authorized users.

FRI0435 Salivary Epidermal Growth Factor (EGF) in SjÖGren's Syndrome: Association between Salivary EGF Levels and the Severity of Intraoral Manifestations

BackgroundXerostomia accompanied in patients with Sjögren's syndrome (SS) relates to reduced salivary flow rate as a result of salivary gland dysfunction. Dry mouth causes various intraoral manifestations such as refractory...

-765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population.

Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

Down-regulation of mechanisms involved in cell transport and maintenance of mucosal integrity in pigs infected with Lawsonia intracellularis.

Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated transcripts, CD163 and CDK1 were novel findings and considered to be important, due to their respective roles in innate immunity and cellular proliferation. Overall, targeted cellular mechanisms included those that are important in epithelial restitution, migration and protection; maintenance of stable inter-epithelial cell relationships; cell transport of nutrients and electrolytes; innate immunity; and cell cycle.

Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

English

Gastric ulcers are mucosal lesions that result from an imbalance between aggressive factors such as acid and pepsin, and defensive mechanisms like gastric mucous, high mucosal blood flow and high mucosal turnover rate that work towards maintenance of mucosal integrity. The aetiology of gastric ulcers is not completely understood and continuous use of anti-ulcer agents leads to many side effects. In the present study, the unsymmetrically substituted urea derivative (1-benzyl-3-(4-methylphenyl) urea) was tested for the anti ulcerogenic activity of alcohol and aspirin induced ulcer models on rats. Ulcer index was calculated by histopathological studies. The test compound at a concentration of 50 and 100 mg/kg exhibited a protective effect on ulcer-induced models in a dose dependent manner, and was comparable with the standard drug ranitidine. These findings indicate that unsymmetrically substituted urea derivative has ulcer protective activity.

Protective role of BLT2 receptor in mouse acute lung injury

Leukotriene B4 (LTB4) is a biologically active lipid mediator for which two G‐protein coupled receptors (GPCR) have been identified, namely BLT1 and BLT2. Although BLT2 has been known as a low affinity LTB4 receptor expressed in epithelial cells of various tissues, the biological roles of BLT2 in vivo remain elusive. We recently identified an endogenously produced fatty acid, 12‐hydroxyheptadecatrienoic acid (12‐HHT) as a high affinity ligand for BLT2, and that BLT2 is important in the maintenance of mucosal integrity and protects intestinal inflammation. Pneumolysin (PLY), a major virulence factor of S. pneumoniae, plays a key role in mortality associated with S. pneumoniae infection by its direct cytotoxic effect to the alveolar epithelium. To investigate the protective role of BLT2 expressed in lung epithelium, we administrated PLY intratracheally to wild type (WT) and BLT2 deficient (BLT2 KO) mice in vivo, and also mouse lung epithelial cell line MLE12 was treated with PLY in vitro. Preliminary experiments showed higher lethality in BLT2 KO mice and the dose‐dependent cytotoxicity in MLE12 that was attenuated in BLT2‐overexpressed cells, suggesting a protective role of BLT2 in S. pneumoniae infection.