Commercial Tobacco Retailers Need to Be Included in Research on Policies Restricting the Sale of Menthol Cigarettes.

INTRODUCTION: Menthol cigarettes are disproportionately marketed and advertised in the commercial tobacco retail environment in Black communities across the United States, contributing to menthol cigarette-related disparities and lower likelihood of successful quitting among Black people who smoke. Policies restricting retail sales of menthol cigarettes are aimed at preventing initiation, promoting quitting, and reducing related disparities. METHODS: Structured phone interview surveys were conducted from January to July 2021 with commercial tobacco retailers in Los Angeles County, California, unincorporated communities with a high percentage of Black residents, eight months after a local policy restricting retail sales of menthol cigarettes and other flavored nicotine and commercial tobacco products became effective on May 20, 2020. Interviews examined menthol cigarette sales restrictions-related knowledge, attitudes, and practices. RESULTS: Among 22 retailers interviewed, most (86.4%) reported having knowledge of the local ban on menthol cigarettes, and more than half (54.5%) reported offering price promotions for menthol cigarettes. Additionally, more than half (54.5%) reported believing customers who buy menthol cigarettes would stop smoking altogether following the ban. CONCLUSIONS: Most retailers reported having knowledge of the menthol ban, yet half reported offering price promotions for menthol cigarettes. Findings suggest retail availability of menthol cigarettes in Los Angeles County unincorporated communities with a high percentage of Black residents, post ban. Public health and policy implications are discussed.

Motivation to Quit Smoking Among Black Adults Residing in Los Angeles County Communities With Menthol Cigarette Sales Restrictions.

Background: Research is needed to identify the determinants of motivation to quit smoking among non-Hispanic Black (NHB) adults who smoke menthol cigarettes and reside in communities covered by menthol cigarette bans. Objectives: This study examined the associations between motivation to quit smoking and a range of individual-level predictors, including measures of demographics, harm/risk perception of menthol cigarettes, and awareness of a ban on menthol cigarettes in Los Angeles County unincorporated communities. Self-identified NHB adults who currently smoke menthol cigarettes (N=50; M=47.2 years; SD=13.7; 46% female) were recruited in Los Angeles County unincorporated communities. Participants completed an interviewer-administered cross-sectional survey between January to September 2021. Results: Participants (74%) reported an annual household income of less than $25,000. Participants' mean age at cigarette initiation was 15.7 years old (SD=5.68). Most (88%) were aware of the ordinance banning menthol cigarette sales. Employing multivariable linear regression analysis, harm/risk perception of menthol cigarettes (B=14.69, p<0.01) and awareness of the local menthol ban (B=26.18, p<0.05) were found to be independently associated with motivation to quit smoking. Conclusions: Findings from this community-based sample suggest that among NHB adults who smoke menthol cigarettes, motivation to quit smoking is influenced by their perception of menthol cigarettes as harmful and awareness of local policy banning the sale of menthol cigarettes. Findings underscore the need for community-centered and culturally grounded interventions to facilitate quitting among NHB adults who smoke in order for communities covered by menthol bans to achieve health equity in reducing preventable racial inequities due to menthol cigarettes.

Hypothetical e-liquid flavor ban and opinions among vape shop retailers in the Greater Los Angeles Area.

INTRODUCTION: Evaluating anticipated responses to flavor bans in the context of vape shops is needed to inform legislation and enforcement. This cross-sectional study examined vape shop retailers' opinions about the potential impacts of an e-liquid flavor ban on shop sales and customer behavior-change intentions. METHODS: From December 2019 to October 2020 we conducted structured interviews over the phone with 46 brick-and-mortar vape shop retailers in the Greater Los Angeles Area. RESULTS: Most participants were managers (43.5%), followed by owners (26.1%) and clerks (26.1%). More than half (52.2%) reported that sales would drop a lot if flavored e-liquids were banned in all vape shops. Controlling for store position, multivariable linear regression showed that opposition to a hypothetical ban on non-tobacco flavored e-liquids was associated with participants' opinions that customers would likely not purchase tobacco flavored e-liquids (b= -0.44, p<0.01), and would likely use combustible tobacco products (b=0.47, p<0.05). CONCLUSIONS: In this cross-sectional study, vape shop retailers in the Greater Los Angeles Area reported that if a ban on non-tobacco e-liquid flavors occurred, they would oppose strongly, and that a ban would have a negative impact on their shop (e.g. loss in sales) and customer behavior (e.g. would replace vaping with smoking combustible tobacco products). Implications for research and practice are discussed.

Whole Genome Sequence of Lactiplantibacillus plantarum HOM3204 and Its Antioxidant Effect on D-Galactose-Induced Aging in Mice.

Lactiplantibacillus plantarum, previously named Lactobacillus plantarum, is a facultative, homofermentative lactic acid bacterium widely distributed in nature. Several Lpb. plantarum strains have been demonstrated to possess good probiotic properties, and Lpb. plantarum HOM3204 is a potential probiotic strain isolated from homemade pickled cabbage plants. In this study, whole-genome sequencing was performed to acquire genetic information and predict the function of HOM3204, which has a circular chromosome of 3,232,697 bp and two plasmids of 48,573 and 17,060 bp, respectively. Moreover, various oxidative stress-related genes were identified in the strain, and its antioxidant activity was evaluated in vitro and in vivo. Compared to reference strains, the intracellular cell-free extracts of Lpb. plantarum HOM3204 at a dose of 1010 colony-forming units (CFU)/ml in vitro exhibited stronger antioxidant properties, such as total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging rate, superoxide dismutase activity, and glutathione (GSH) content. Daily administration of 109 CFU Lpb. plantarum HOM3204 for 45 days significantly improved the antioxidant function by increasing the glutathione peroxidase activity in the whole blood and GSH concentration in the livers of D-galactose-induced aging mice. These results suggest that Lpb. plantarum HOM3204 can potentially be used as a food ingredient with good antioxidant properties.

A content analysis of website marketing for cooling flavored e-liquids in a sample of brick-and-mortar vape shops in the Greater Los Angeles area.

INTRODUCTION: Menthol is a characterizing flavor in combustible cigarettes and electronic nicotine delivery systems (ENDS). E-liquids are recognized as an important reason for ENDS use. Yet, compared to menthol cigarettes, menthol flavored e-liquids and other cooling flavors, including mint and 'ice' for ENDS, are an understudied area of investigation. The present study examined cooling flavored e-liquid website marketing among brick-and-mortar vape shops in Greater Los Angeles Area. METHODS: A total of 104 brick-and-mortar vape shops were identified, and 38 had active websites. Over a 30-day period (28 September - 28 October 2020), we collected marketing for all flavored refillable e-liquids (photos/images) from each website. Data were collected for 1330 products. Only refillable e-liquid bottles were selected for this study, excluding prefilled pod vapes and disposable vapes. Each e-liquid per website was coded (e.g. menthol or not) and grouped into categories (e.g. type of menthol). The three flavor descriptor categories that the e-liquids were grouped into were menthol, mint, or ice. An 'other' category was also created for identified e-liquids with flavor descriptors that did not mention menthol, mint, or ice. RESULTS: A total of 1330 e-liquid flavors were identified from 38 active websites. Among them, 219 were coded as menthol/mint/ice flavor e-liquids. Frequencies included ice/iced/icy (n=123; 56%), menthol (n=32; 15%), mint (n=23; 11%), and other (n=41; 19%). Of the 123 ice-flavor e-liquids, 70.3% (n=83) were in combination with fruit (e.g. 'Apple Ice', 'Grape Iced', 'Icy Mango'). Of the 32 menthol-flavored e-liquids, 63.3% (n=19) were in combination with fruit (e.g. 'Dragon Fruit Menthol', 'Blue Raspberry Menthol', 'Fresh Peach Menthol'). Flavors in the other category were ice-related flavor descriptors (e.g. 'Arctic Air', 'Brain Freeze', 'Frozen Hulk Tears'). CONCLUSIONS: Brick-and-mortar vape shops in the Greater Los Angeles Area market a variety of cooling flavor e-liquids on their websites. Such marketing focused largely on ice fruit flavor combinations. Future research is needed to understand how exposure to and appeal of cooling flavored e-liquid marketing differs among diverse consumer groups, including adult menthol cigarette smokers and non-smoking youth.

Marketing claims on websites of brick-and-mortar vape shops in the Greater Los Angeles area.

INTRODUCTION: Brick-and-mortar vape shops have increased in recent years, but there is limited research on the types of marketing claims consumers are exposed to on their websites - a dominant channel for marketing electronic nicotine delivery systems (ENDS). We investigated the websites of vape shop retailers in the Greater Los Angeles Area to describe their ENDS marketing claims. METHODS: Data collection occurred between 25 March and 20 June 2020. Of the 104 brick-and-mortar vape shops identified, 37 were found to have active websites. Rules were established to analyze website content. ENDS Marketing Claims were coded as the presence or absence of: 1) a direct claim of ENDS as a quitting aid; 2) a disclaimer that ENDS are not approved as smoking cessation devices (i.e. ENDS products are not FDA-approved for smoking cessation); 3) a direct claim of ENDS as healthier/safer than combustible cigarettes; and 4) direct claims regarding social benefits, including that ENDS are less expensive, can be used in more places, are cleaner or less messy/smelly, and are more socially accepted than combustible cigarettes. RESULTS: Smoking cessation-related benefits were claimed most frequently (43%), followed by health-related claims (30%), and disclaimers that ENDS are not approved as smoking cessation devices (24%). More than half (56.4%) of websites had an age restriction, requiring the user to click on a box to state that they were aged ≥21 years to view the site. None required proof or outside verification of age. CONCLUSIONS: Brick-and-mortar vape shops in the Greater Los Angeles Area are marketing ENDS on their websites as a healthier alternative to smoking cigarettes. Although half of the websites had an age gate popup that consumers see when they enter the website, action is needed to better enforce age restriction on access to vape shop websites. Utility for smoking cessation was claimed most frequently, followed by the claims of healthier alternatives to smoking cigarettes, and disclaimers that ENDS are not approved as smoking cessation devices. We discuss implications for tobacco regulatory policy.

Perceptions of E-cigarettes and Flavor Restrictions among Tobacco Retailers in Los Angeles.

Objectives: In this study, we examined tobacco retailers' perceptions of e-cigarettes and associations with in-store availability of e-cigarettes. Methods: Retailers (N = 700) in multiple, racial/ethnic neighborhoods (black/African-American, N = 200); Hispanic/Latino, N = 200; white American, N = 200; Korean American, N = 100) in Los Angeles County participated in on-site interviews and store observations. Results: Controlling for individual and racial/ethnic neighborhood factors, retailers in majority-white neighborhoods had significantly higher odds of selling e-cigarettes and flavored e-cigarettes than retailers located in Hispanic/Latino (p < .001, OR = 0.14, 95% CI = 0.08-0.25; p < .001, OR = 0.19, 95% CI = 0.11-0.33) and Korean American (p < .05, OR = 0.21, 95% CI = 0.12-0.37; p < .05, OR = 0.21, 95% CI = 0.12-0.39) neighborhoods. Perceptions of e-cigarettes as being completely safe/safer than cigarettes were significantly associated with availability of flavored e-cigarettes (p < .05, OR = 2.03, 95% CI = 1.04-3.97); and opposition to flavored e-cigarette restrictions was marginally significantly associated with availability of flavored e-cigarettes (p < .10, OR = 1.56, 95% CI = 0.96-2.51). Adjusting for store type, perceptions of e-cigarettes as being completely safe/safer than cigarettes were marginally significantly associated with availability of flavored e-cigarettes (p < .10, OR = 1.78, 95% CI = 0.85-3.73). Conclusions: Targeted efforts are warranted for educating retailers and employees in these neighborhoods on the appeal and nicotine dependence potential of e-cigarette use for youth.

Smoking Diffusion through Networks of Diverse, Urban American Adolescents over the High School Period.

This study uses recent data to investigate if smoking initiation diffuses through friendship networks over the high school period and explores if diffusion processes differ across schools. One thousand four hundred and twenty-five racially and ethnically diverse youth from four high schools in Los Angeles were surveyed four times over the high school period from 2010 to 2013. Probit regression models and stochastic actor-based models for network dynamics tested for peer effects on smoking initiation. Friend smoking was found to predict adolescent smoking, and smoking initiation diffused through friendship networks in some but not all of the schools. School differences in smoking rates and the popularity of smokers may be linked to differences in the diffusion of smoking through peer networks. We conclude that there are differences in peer effects on smoking initiation across schools that will be important to account for in network-based smoking interventions.

T3SS effector ExoY reduces inflammasome-related responses by suppressing bacterial motility and delaying activation of NF-κB and caspase-1.

Type III-secreted effectors are essential for modulating host immune responses during the pathogenesis of Pseudomonas aeruginosa infections. Little is known about the impact of one of the effectors, ExoY, on inflammasome activation, which results in IL-1ß production and pyroptotic cell death. In this study, we found that transcriptional expression of Il-1ß was induced to a lesser extent in response to an exoY-harboring strain than to a deleted mutant. This suppressive effect of ExoY was verified by complementation assay as well as by direct translocation of exoY into host cells. In addition to the production of IL-1ß, pyroptotic cell death was also diminished in response to an exoY-harboring strain. These inflammasome responses were mediated by the adenylate cyclase activity of ExoY, which plays a role in delaying the activation of NF-κB and caspase-1, a key component of inflammasome-mediated responses. Moreover, the negative effects of ExoY on these responses were in part conferred by the suppression of bacterial motility, which could reduce the degree of bacterial contact with cells. Together, these results demonstrate that the adenylate cyclase activity of P. aeruginosa ExoY can reduce inflammasome-related responses by influencing both the host and the bacterium itself by delaying the activation of inflammatory pathways and suppressing bacterial motility.

Using Ecological Momentary Assessment to Identify Common Smoking Situations Among Korean American Emerging Adults.

The present study provides detailed contextual information about smoking habits among young Korean American smokers with the goal of characterizing situations where they are most at risk for smoking. Relevant situational factors included location, social context, concurrent activities, time of day, affective states, and food and beverage consumption. Using ecological momentary assessment (EMA) over 7 days, participants (N = 78) were instructed to respond to smoking prompts (n = 2614) and non-smoking prompts (n = 2136) randomly scheduled throughout the day. At each prompt, participants completed a short survey about immediate contextual factors. We used multilevel models to evaluate the association between contextual factors and smoking and further explored the distribution of smoking locations and concurrent activities across each social context and reason for smoking. Compared to non-smoking events, smoking events were associated with being outside, the presence of Korean friends, socializing, consuming alcohol, and experiencing more stress relative to one's average stress level (all ps < .01). Further analyses involving only smoking events showed that when participants smoked alone, they were most commonly at home (50 %) and most often studying/working (28 %). When smoking with Korean friends, participants were most often outside (38 %) and socializing (54 %). When smoking to reduce craving, participants were most often at home (39 %) and studying/working (25 %). To our knowledge, this is the first study to provide detailed descriptions of real-time smoking contexts among young Korean American smokers. Information with this level of granularity is needed to develop effective just-in-time adaptive interventions (JITAIs) for smoking cessation.

Parent, peer, and executive function relationships to early adolescent e-cigarette use: a substance use pathway?

INTRODUCTION: Little is known about influences on e-cigarette use among early adolescents. This study examined influences that have been previously found to be associated with gateway drug use in adolescents: demographic (age, gender, ethnicity, free lunch), social contextual influences of parents and peers, and executive function deficits (EF). METHODS: A cross-sectional survey was administered to 410 7th grade students from two diverse school districts in Southern California (M age;=12.4years, 48.3% female, 34.9% on free lunch (low socioeconomic status), 45.1% White, 25.4% Hispanic/Latino, 14.9% Mixed/bi-racial.) Logistic regression analyses examined influences of demographic, parent e-cigarette ownership and peer use, and EF on lifetime e-cigarette, and gateway drug use (cigarette and/or alcohol use). RESULTS: Lifetime use prevalence was 11.0% for e-cigarettes, 6.8% for cigarettes, and 38.1% for alcohol. Free lunch and age were marginally related to e-cigarette use (p<.10). Parent e-cigarette ownership was associated with use of all substances, while peer use was associated with gateway drug use (p's<.05-.001). EF deficits were associated with use of all substances five times more likely than others to use e-cigarettes and over twice as likely to use gateway drugs. CONCLUSIONS: E-cigarette and gateway drug use may have common underlying risk factors in early adolescence, including parent and peer modeling of substance use, as well as EF deficits. Future research is needed to examine longitudinal relationships of demographics, parent and peer modeling, and EF deficits to e-cigarette use in larger samples, trajectories of e-cigarette use compared to use of other substances, and the potential of EF skills training programs to prevent e-cigarette use.

Pseudomonas aeruginosa-induced IL-1ß production is inhibited by Sophora flavescens via the NF-κB/inflammasome pathways.

The proinflammatory cytokine interleukin-1ß plays an important role in protecting the host against airway infection; however, it can also trigger a massive influx of neutrophils into the airways, causing tissue damage. Anti-inflammatory treatments are particularly in demand for patients suffering from chronic inflammatory diseases. Sophora flavescens is a traditional herbal medicine used to reduce inflammation, but no study has examined its ability to block IL-1ß production. Here, we show that S. flavescens reduced the Pseudomonas aeruginosa-induced expression of IL-1ß by lung epithelial cells and macrophages. S. flavescens was also effective at reducing IL-1ß production induced by either Staphylococcus aureus or phorbol 12-myristate 13-acetate, indicating that the effect is generalizable to diverse inflammatory stimuli. In addition, S. flavescens blocked the phosphorylation of IKKα/ß, key upstream kinases involved in the degradation of IκBα, and the cleavage of caspase-1, a key component of the inflammasome. Thus, this study demonstrates that S. flavescens exerts its anti-inflammatory effects by blocking P. aeruginosa-mediated NF-κB/inflammasome activation and the subsequent production of IL-1ß.

CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis.

Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

Momentary negative moods and being with friends precede cigarette use among Korean American emerging adults.

INTRODUCTION: The objective of this study was to determine contextual antecedents to smoking among Korean American emerging adult (KAEA) smokers using ecological momentary assessment. Based on extant theory and data documenting the importance of negative affect (NA) and social context, we examined the extent to which being with friends and NA independently and concomitantly were associated with the likelihood of subsequent smoking, over and beyond other known situational correlates of smoking. METHODS: Twenty-two KAEA daily smokers recorded their smoking events in real time and participated in short surveys implemented on mobile phones for 7 days. Individual, interpersonal, and situational contexts immediately preceding and during smoking events were examined in comparison to nonsmoking events using a within-subject modeling approach. RESULTS: Both NA and being with friends independently were correlated with increased likelihood of smoking. We also found an interaction showing that the effects of NA on smoking were significant only in presence of friends. CONCLUSIONS: Unlike more established smokers, these younger smokers may be strongly influenced by peer contexts as well as unpleasant affect. The interaction between social contexts and NA highlights a potential window for intervention for the population of KAEA smokers.

The interaction of social networks and child obesity prevention program effects: the pathways trial.

OBJECTIVE: Social network analysis was used to examine whether peer influence from one's social networks moderates obesity prevention program effects on obesity-related behaviors: healthful and unhealthful. METHODS: Participants included 557 children residing in Southern California. The survey assessed health-promoting behaviors (i.e., physical activity at school, physical activity outside of school, and fruit and vegetable intake), as well as unhealthful behaviors (high-calorie, low-nutrient intake and sedentary activity), and peer exposure calculated from social network nominations as indicators of peer influence. Multilevel models were conducted separately on outcomes predicted by program participation, peer exposure, and program participation by peer exposure. RESULTS: Results indicated that peer exposure was positively associated with one's own healthful and unhealthful behaviors. Program participation effects were moderated by peer influence, but only when unhealthful peer influence was present. Results suggest that peer influence can diminish or amplify prevention programs CONCLUSION: Future interventions should consider peer-led components to promote healthful influence of peers on healthful and unhealthful behaviors, and programs should be mindful that their effects are moderated by social networks.

Pseudomonas aeruginosa-dependent upregulation of TLR2 influences host responses to a secondary Staphylococcus aureus infection.

The clinical impact of polymicrobial infections has received increasing attention from the medical community. However, the potential effects of Pseudomonas aeruginosa infection on the development of host responses against Gram-positive bacteria, such as Staphylococcus aureus, are unknown. Here, P. aeruginosa infection was found to induce the expression of Toll-like receptor 2 (TLR2), which plays a dominant role in sensing pathogen-associated molecular patterns (PAMPs) expressed by Gram-positive bacteria. P. aeruginosa-dependent upregulation of TLR2 was not mediated by flagellin, or by the type III (T3SS) or type VI (T6SS) secretion systems, but was upregulated by lipopolysaccharide (LPS). Upregulation of TLR2 influenced the magnitude of proinflammatory responses to the secondary S. aureus infection, but there was no clear effect on phagocytosis of S. aureus by macrophages. Taken together, the results of this study demonstrate that P. aeruginosa infection results in the upregulation of TLR2 expression, subsequently enhancing innate immune responses against a secondary S. aureus infection.

Pneumolysin-mediated expression of ß-defensin 2 is coordinated by p38 MAP kinase-MKP1 in human airway cells.

Antimicrobial peptides act as important innate immune defense mediators against invading microbes such as Streptococcus pneumoniae. Among a number of antimicrobial peptides, ß-defensin 2 (BD2) has strong antimicrobial activity against S. pneumoniae. However, little is known about the molecular signaling mechanisms leading to the BD2 expression. Here, we report that BD2 is strongly induced by S. pneumoniae in human airway cells including human middle-ear cells. Among diverse pneumococcal virulence factors, pneumolysin is required for inducing BD2 whose expression is under the control of p38 mitogen-activated protein kinase (MAPK). Pneumolysin also selectively regulates the expression of MAPK phosphatase 1 (MKP1), which inhibits the p38 signaling pathway, thereby leading to upregulation of BD2 to mount an effective defense against S. pneumoniae infection. These results provide novel insights into the molecular mechanisms underlying the coordinative regulation of BD2 expression via p38-MKP1 in the pathogenesis of airway infectious diseases.

Up-regulation of human bradykinin B1 receptor by secreted components of Pseudomonas aeruginosa via a NF-κB pathway in epithelial cells.

Pulmonary epithelial cells produce neutrophil chemotactic activity in response to pathogenic bacterial infections, resulting in neutrophil migration to infection sites. Elicited neutrophils in the inflamed tissues were found to be dependent on bradykinin B1 receptor (B1R), which shows high affinity for the active metabolites derived from bradykinin. Thus, the up-regulation of bradykinin and B1R expression represents an important host defense response against invading microbes such as Pseudomonas aeruginosa. However, the effect of P. aeruginosa on the expression of B1R remains unclear, while P. aeruginosa infection is known to stimulate the production of bradykinin. Here, we report that human B1R (hB1R) transcription is up-regulated in host cells co-cultured with P. aeruginosa. Components secreted from P. aeruginosa play a major role in the up-regulation, and the secretion of the components is not controlled by either type III secretion system or quorum sensing. Moreover, the B1R induction is mediated by a NF-κB signaling pathway in human lung epithelial cells. Taken together, this study demonstrates that P. aeruginosa is capable of up-regulating hB1R expression via the NF-κB signaling pathway.

Up-regulation of bradykinin B2 receptor by Pseudomonas aeruginosa via the NF-κB pathway.

As the first line of host defense, inflammatory responses in response to bacterial infection are initiated by the production of a range of mediators. Infection of Pseudomonas aeruginosa has been shown to stimulate the production of bradykinin (BK), which is known as a universal mediator for the induction of inflammatory reaction via the predominant interaction with the bradykinin B2 receptor (B2R). Thus, the interaction between BK and B2R represents an important host innate response against invading P. aeruginosa. However, the contribution of P. aeruginosa to the up-regulation of B2R expression remains unclear. Here, we report that P. aeruginosa is potent in inducing the expression of B2R at the mRNA and protein levels in a dose- and time-dependent manner. Components produced and secreted from P. aeruginosa could play an essential role in inducing B2R expression, and the secreted components are not under the control of Type III secretion system or quorum sensing. B2R expression in response to P. aeruginosa is mediated by the induction of cellular signaling that leads to the activation of transcription factor NF-κB. Thus, this study demonstrates that P. aeruginosa is able to up-regulate the expression of B2R during infection via the NF-κB signaling pathway.

Context-dependent transcriptional regulations between signal transduction pathways.

BACKGROUND: Cells coordinate their metabolism, proliferation, and cellular communication according to environmental cues through signal transduction. Because signal transduction has a primary role in cellular processes, many experimental techniques and approaches have emerged to discover the molecular components and dynamics that are dependent on cellular contexts. However, omics approaches based on genome-wide expression analysis data comparing one differing condition (e.g. complex disease patients and normal subjects) did not investigate the dynamics and inter-pathway cross-communication that are dependent on cellular contexts. Therefore, we introduce a new computational omics approach for discovering signal transduction pathways regulated by transcription and transcriptional regulations between pathways in signaling networks that are dependent on cellular contexts, especially focusing on a transcription-mediated mechanism of inter-pathway cross-communication. RESULTS: Applied to dendritic cells treated with lipopolysaccharide, our analysis well depicted how dendritic cells respond to the treatment through transcriptional regulations between signal transduction pathways in dendritic cell maturation and T cell activation. CONCLUSIONS: Our new approach helps to understand the underlying biological phenomenon of expression data (e.g. complex diseases such as cancer) by providing a graphical network which shows transcriptional regulations between signal transduction pathways. The software programs are available upon request.