TRP channels as potential drug targets

Calcium (Ca2+) is an ubiquitous intracellular signal that is responsible for a plethora of cellular processes including fertilization, secretion, contraction, neuronal signaling and learning. In addition, changes in intracellular Ca2+ have been known to influence cell proliferation and differentiation for more than three decades. Recent studies have indicated that members of the transient receptor potential (TRP) family of ion channels which respond to many different modes of stimulation both from within and outside the cell may be a primary mode of cation and Ca2+ entry into cells and may have roles in growth control. Moreover, changes in the expression of these channels may contribute to certain cancers. In the following, recent results concerning the expression and function of members of this family of ion channels are summarized.     

When a TRP goes bad: Transient receptor potential channels in addiction

Drug addiction is a psychiatric disease state, wherein a drug is impulsively and compulsively self-administered despite negative consequences. This repeated administration results in permanent changes to nervous system physiology and architecture. The molecular pathways affected by addictive drugs are complex and inter-dependent on each other. Recently, various new proteins and protein families have been discovered to play a role in drug abuse. Emerging players in this phenomenon include TRP (Transient Receptor Potential) family channels, which are primarily known to function in sensory systems. Several TRP family channels identified in both vertebrates and invertebrates are involved in psychostimulant-induced plasticity, suggesting their involvement in drug dependence. This review summarizes various observations, both from studies in humans and other organisms, which support a role for these channels in the development of drug-related behaviors.     

Transient receptor potential channels in Alzheimer's disease

Cognitive impairment and emotional disturbances in Alzheimer's disease (AD) result from the degeneration of synapses and neuronal death in the limbic system and associated regions of the cerebral cortex. An alteration in the proteolytic processing of the amyloid precursor protein (APP) results in increased production and accumulation of amyloid beta-peptide (Abeta) in the brain. Abeta can render neurons vulnerable to excitotoxicity and apoptosis by disruption of cellular Ca(2+) homeostasis and neurotoxic factors including reactive oxygen species (ROS), nitric oxide (NO), and cytokines. Many lines of evidence have suggested that transient receptor potential (TRP) channels consisting of six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) are involved in Ca(2+) homeostasis disruption. Thus, emerging evidence of the pathophysiological role of TRP channels has yielded promising candidates for molecular entities mediating Ca(2+) homeostasis disruption in AD. In this review, we focus on the TRP channels in AD and highlight some TRP "suspects" for which a role in AD can be anticipated. An understanding of the involvement of TRP channels in AD may lead to the development of new target therapies.     

Transient receptor potential genes, smoking, occupational exposures and cough in adults

Background

Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant exposures on cough.

Methods

Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model.

Results

Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10^-6) and usual cough (9-SNP haplotype: p-global = 4.5 × 10^-6). Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p < 0.05). Four polymorphisms in TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p < 0.05).

Conclusions

TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.     

Establishing life is a calcium-dependent TRiP: Transient receptor potential channels in reproduction

Calcium plays a key role in many different steps of the reproduction process, from germ cell maturation to placental development. However, the exact function and regulation of calcium throughout subsequent reproductive events remains rather enigmatic. Successful pregnancy requires the establishment of a complex dialogue between the implanting embryo and the endometrium. On the one hand, endometrial cell will undergo massive changes to support an implanting embryo, including stromal cell decidualization. On the other hand, trophoblast cells from the trophectoderm surrounding the inner cell mass will differentiate and acquire new functions such as hormone secretion, invasion and migration. The need for calcium in the different gestational processes implicates the presence of specialized ion channels to regulate calcium homeostasis. The superfamily of transient receptor potential (TRP) channels is a class of calcium permeable ion channels that is involved in the transformation of extracellular stimuli into the influx of calcium, inducing and coordinating underlying signaling pathways. Although the necessity of calcium throughout reproduction cannot be negated, the expression and functionality of TRP channels throughout gestation remains elusive. This review provides an overview of the current evidence regarding the expression and function of TRP channels in reproduction.     

慢性阻塞性肺疾病急性加重期患者痰液微生物组分析

通过高通量测序分析慢性阻塞性肺疾病急性加重期（AECOPD）、AECOPD合并哮喘、AECOPD合并支气管扩张患者的痰液菌群组成特征及其差异,寻找影响疾病严重程度的关键微生物。

收集西南医科大学附属医院呼吸与危重症医学科收治的AECOPD患者（n=11）、AECOPD合并支气管扩张患者（n=5）、AECOPD合并哮喘患者（n=5）的痰液样本进行16S rDNA测序分析。利用Illumina HiSeq 2500测序仪测序后的数据进行生物信息学分析。

AECOPD患者、AECOPD合并支气管扩张患者、AECOPD合并哮喘患者痰液菌群主要由厚壁菌门、变形菌门、嗜血杆菌属、链球菌属组成。AECOPD合并哮喘患者厚壁菌门丰度显著低于AECOPD患者（Q=0.781,P=0.049）,AECOPD合并支气管扩张患者罗氏菌属丰度显著低于AECOPD患者（Q=0.693,P=0.008）。AECOPD合并哮喘患者和AECOPD合并支气管扩张患者痰菌群差异增大。肺功能受损较重者嗜血杆菌属、巴斯德菌科增加,而轻度肺功能受损者莫拉菌属增加。

AECOPD与AECOPD合并支气管扩张或合并哮喘患者痰液菌群组成有差异,痰液菌群组成可能影响GOLD分级。

     

慢性阻塞性肺疾病急性加重期病原学及细菌药性分析

目的:探讨慢性阻塞性肺疾病急性加重期病原学特点及细菌耐药情况,为临床合理使用抗生素提供科学依据。方法:回顾性分析我院呼吸内科和老年学科2008年1月-2009年1月563例慢性阻塞性肺疾病(急性加重期)住院患者痰培养及药敏试验结果。结果:563例患者中检出阳性结果205例,检出率为36.41%。其中G+菌46例、G-菌119例、真菌40例。G+菌以金黄色葡萄球菌最多(14例),其次为表皮葡萄球菌和草绿色链球菌;G-菌以铜绿假单胞菌最多(37例),其次为克雷伯菌;真菌以白色念珠菌最多(20例)。G-杆菌对氨苄西林、哌拉西林、头孢唑啉、复方新诺明耐药严重,对亚胺培南、含β-内酰胺酶抑制剂的联合制剂较敏感。金黄色葡萄球菌对多种抗生素严重耐药,对万古霉素、亚胺培南较敏感。真菌对氟康唑敏感占50.81%,对伊曲康唑敏感占30.12%,对酮康唑敏感占30.83%,对5-氟胞嘧啶敏感占10.74%。结论:慢性阻塞性肺疾病急性加重期以G-为主,真菌感染有增多趋势,病原菌呈现多重耐药现象。     

Transient receptor potential channels meet phosphoinositides

Transient receptor potential (TRP) cation channels are unique cellular sensors that are involved in multiple cellular functions, ranging from transduction of sensory signals to the regulation of Ca²⁺ and Mg²⁺ homoeostasis. Malfunctioning of TRP channels is now recognized as the cause of several hereditary and acquired human diseases. At the time of cloning of the first Drosophila TRP channel, a close connection between gating and phosphatidylinositol phosphates (PIPs) was already recognized. In this review, we summarize current knowledge about the mechanisms of interaction between TRP channels and PIPs, and discuss the possible functional implications of TRP–PIP interactions to human physiology and pathophysiology.     

The transient receptor potential (TRP) channel TRPC3 TRP domain and AMP-activated protein kinase binding site are required for TRPC3 activation by erythropoietin

Modulation of intracellular calcium ([Ca(2+)](i)) by erythropoietin (Epo) is an important signaling pathway controlling erythroid proliferation and differentiation. Transient receptor potential (TRP) channels TRPC3 and homologous TRPC6 are expressed on normal human erythroid precursors, but Epo stimulates an increase in [Ca(2+)](i) through TRPC3 but not TRPC6. Here, the role of specific domains in the different responsiveness of TRPC3 and TRPC6 to erythropoietin was explored. TRPC3 and TRPC6 TRP domains differ in seven amino acids. Substitution of five amino acids (DDKPS) in the TRPC3 TRP domain with those of TRPC6 (EERVN) abolished the Epo-stimulated increase in [Ca(2+)](i). Substitution of EERVN in TRPC6 TRP domain with DDKPS in TRPC3 did not confer Epo responsiveness. However, substitution of TRPC6 TRP with DDKPS from TRPC3 TRP, as well as swapping the TRPC6 distal C terminus (C2) with that of TRPC3, resulted in a chimeric TRPC6 channel with Epo responsiveness similar to TRPC3. Substitution of TRPC6 with TRPC3 TRP and the putative TRPC3 C-terminal AMP-activated protein kinase (AMPK) binding site straddling TRPC3 C1/C2 also resulted in TRPC6 activation. In contrast, substitution of the TRPC3 C-terminal leucine zipper motif or TRPC3 phosphorylation sites Ser-681, Ser-708, or Ser-764 with TRPC6 sequence did not affect TRPC3 Epo responsiveness. TRPC3, but not TRPC6, and TRPC6 chimeras expressing TRPC3 C2 showed significantly increased plasma membrane insertion following Epo stimulation and substantial cytoskeletal association. The TRPC3 TRP domain, distal C terminus (C2), and AMPK binding site are critical elements that confer Epo responsiveness. In particular, the TRPC3 C2 and AMPK site are essential for association of TRPC3 with the cytoskeleton and increased channel translocation to the cell surface in response to Epo stimulation.     

Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study

Background

Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.

Methods

We divided 2703 GOLD 1–4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).

Results

There were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV₁%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.

Conclusions

Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV₁%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.     

慢性呼吸道疾病患者呼吸道微生物群研究进展

过去认为健康人肺部是无菌的,对疾病状态下呼吸道菌群的研究依赖传统培养技术。近年来,DNA测序技术应用于呼吸道标本的微生物检测,发现健康肺部存在复杂的微生物群。越来越多的证据表明,呼吸道微生物群在多种慢性呼吸道疾病发生和发展过程中扮演重要角色,与哮喘、慢性阻塞性肺病等疾病的临床表现、急性加重及预后相关。通过比较急性加重期与稳定期患者的呼吸道标本微生物群,形成了新的疾病假说,阐释了慢性呼吸道疾病急性加重的微生物学基础。未来对微生物测序数据的深度挖掘及基于临床问题的研究,有望为慢性呼吸道疾病的治疗提供新的靶点。     

慢性阻塞性肺病患者巨噬细胞功能与受体表达的关系研究

目的:研究慢性阻塞性肺病(COPD)患者气道巨噬细胞功能变化及其与受体表达的相关性。方法:将COPD患者84例按病情分为轻中度组44例,重度组40例,选取同期健康体检者40例作为对照组,获取3组诱导痰,分离痰巨噬细胞,检测3组吞噬荧光标记曲霉孢子的吞噬指数(PI),采用实时定量反转录PCR法检测3组吞噬相关受体的表达。结果:轻中度组与重度组细胞总数均多于对照组,而巨噬细胞比例却显著下降(P0.05);轻中度组与重度组巨噬细胞吞噬功能均受到抑制,3组PI比较差异有统计学意义(P0.05);3组巨噬细胞胶原结构清道夫系统(MARCO)、清道夫受体A1(SR-A1)表达量比较差异不明显(P0.05);轻中度组与对照组Toll样受体4(TLR4)表达量比较差异不明显,但重度组TLR4表达上调,与轻中度组、对照组比较差异有统计学意义(P0.05);3组MUC5A、AQP5表达量比较差异显著(P0.05);巨噬细胞PI与TLR4、黏蛋白5AC(MUC5A)表达量呈负相关(P0.05),与水通道蛋白5(AQP5)表达量呈正相关(P0.05)。结论:COPD患者巨噬细胞占细胞总数的比例下降,其吞噬功能也受到抑制,其机制可能与TLR4、MUC5A表达上调及AQP5表达下调等有关。     

Transient receptor potential canonical channels are required for in vitro endothelial tube formation

In endothelial cells Ca(2+) entry is an essential component of the Ca(2+) signal that takes place during processes such as cell proliferation or angiogenesis. Ca(2+) influx occurs via the store-operated Ca(2+) entry pathway, involving stromal interaction molecule-1 (STIM1) and Orai1, but also through channels gated by second messengers like the transient receptor potential canonical (TRPC) channels. The human umbilical vein-derived endothelial cell line EA.hy926 expressed STIM1 and Orai1 as well as several TRPC channels. By invalidating each of these molecules, we showed that TRPC3, TRPC4, and TRPC5 are essential for the formation of tubular structures observed after EA.hy926 cells were plated on Matrigel. On the contrary, the silencing of STIM1 or Orai1 did not prevent tubulogenesis. Soon after being plated on Matrigel, the cells displayed spontaneous Ca(2+) oscillations that were strongly reduced by treatment with siRNA against TRPC3, TRPC4, or TRPC5, but not siRNA against STIM1 or Orai1. Furthermore, we showed that cell proliferation was reduced upon siRNA treatment against TRPC3, TRPC5, and Orai1 channels, whereas the knockdown of STIM1 had no effect. On primary human umbilical vein endothelial cells, TRPC1, TRPC4, and STIM1 are involved in tube formation, whereas Orai1 has no effect. These data showed that TRPC channels are essential for in vitro tubulogenesis, both on endothelial cell line and on primary endothelial cells.     

Interplay between TRP channels and the cytoskeleton in health and disease

Transient receptor potential (TRP) channels are a family of cation channels that play a key role in ion homeostasis and cell volume regulation. In addition, TRP channels are considered universal integrators of sensory information required for taste, vision, hearing, touch, temperature, and the detection of mechanical force. Seminal investigations exploring the molecular mechanisms of phototransduction in Drosophila have demonstrated that TRP channels operate within macromolecular complexes closely associated with the cytoskeleton. More recent evidence shows that mammalian TRP channels similarly connect to the cytoskeleton to affect cytoskeletal organization and cell adhesion via ion-transport-dependent and -independent mechanisms. In this review, we discuss new insights into the interplay between TRP channels and the cytoskeleton and provide recent examples of such interactions in different physiological systems.     

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal transduction.     

血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性分析

目的探讨血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性。方法将我院收治的94例COPD稳定期患者,根据心脏彩超检查明确合并慢性肺心病患者分为观察组46例,单纯COPD患者分为对照组48例,采用化学发光法测定两组患者血浆NT-proBNP水平,心脏彩超检查两组患者右心室前壁厚度、右心室舒张末期内径、左室射血分数、主肺动脉宽度、肺动脉压,并进行比较。结果与对照组比较,观察组血浆NT-proBNP水平明显升高(P0.05),右心室前壁厚度、右心室舒张末期内径、主肺动脉宽度、肺动脉压明显升高(P0.05)。血浆NT-proBNP水平与肺动脉压成明显正相关(r=-0.284,P0.01)。结论 COPD合并慢性肺心病患者血浆NT-proBNP水平升高,有助于评估肺动脉高压的严重程度。     

慢性阻塞性肺病急性加重期下呼吸道病原菌感染及药敏结果分析

目的探讨慢性阻塞性肺病急性加重期(AECOPD)下呼吸道病原菌群的分布及分析药敏试验结果。方法对仙居县人民医院呼吸病房收治的128例AECOPD患者的痰细菌培养和药敏试验结果进行分析。结果 AECOPD患者感染的病原菌中,革兰阴性杆菌占61.95%,以铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌为主;革兰阳性球菌占21.43%,以金黄色葡萄球菌、粪肠球菌为主;真菌占14.88%;2种以上病原菌混合感染占20.31%。体外药敏试验发现:亚胺培南对大部分革兰阴性杆菌有较好敏感性,万古霉素对大部分革兰阳性球菌有较好敏感性,检出的真菌对氟胞嘧啶、两性霉素、氟康唑、依曲康唑均保持较高敏感性。结论 AECOPD患者下呼吸道感染病原菌以革兰阴性杆菌为主,真菌感染率和混合感染率较高,应引起重视,应根据药敏结果合理选用抗菌药物。     

Modulation of cellular membrane properties as a potential therapeutic strategy to counter lipointoxication in obstructive pulmonary diseases

Maintaining the equilibrium between saturated and unsaturated fatty acids within membrane phospholipids (PLs) is crucial to sustain the optimal membrane biophysical properties, compatible with selective organelle-based processes. Lipointoxication is a pathological condition under which saturated PLs tend to accumulate within the cell at the expense of unsaturated species, with major impacts on organelle function. Here, we show that human bronchial epithelial cells extracted from lungs of patients with Obstructive Pulmonary Diseases (OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a characteristic lipointoxication signature, with excessive amounts of saturated PLs. Reconstitution of this signature in cellulo and in silico revealed that such an imbalance results in altered membrane properties and in a dramatic disorganization of the intracellular network of bronchial epithelial cells, in a process which can account for several OPD traits. Such features include Endoplasmic Reticulum-stress, constitutive IL8 secretion, bronchoconstriction and, ultimately, epithelial cell death by apoptosis. We also demonstrate that a recently-identified lipid-like molecule, which has been shown to behave as a “membrane-reshaper”, counters all the lipointoxication hallmarks tested. Altogether, these insights highlight the modulation of membrane properties as a potential new strategy to heal and prevent highly detrimental symptoms associated with OPDs.     

Leptin, adiponectin and pulmonary diseases

Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority of the evidence among children however suggests that systemic leptin may be associated with greater asthma prevalence and severity, particularly among prepubertal boys and peripubertal/postpubertal girls. Systemic and airway leptin concentrations may also be disproportionately higher in chronic obstructive pulmonary disease (COPD) patients, particularly among women, and reflect greater airway inflammation and disease severity. Quite like leptin, the association between systemic and airway adiponectin and asthma in humans is also controversial. Some but not all studies, demonstrate that serum adiponectin concentrations are protective against asthma among premenopausal women and peripubertal girls. On the other hand, serum adiponectin concentrations are inversely associated with asthma severity among boys but positively associated among men. Further, systemic and airway adiponectin concentrations are higher in COPD patients than controls, as demonstrated by case-control studies of men. Systemic adiponectin is also positively associated with lung function in healthy adults but inversely associated with lung function in subjects with COPD. It is therefore possible that pro-inflammatory effects of adiponectin dominate under certain physiologic conditions and anti-inflammatory effects under others. The adipokine-lung disease literature has critical gaps that include a lack of adequately powered longitudinal or weight-intervention studies; inadequate adjustment for confounding effect of obesity; and unclear understanding of potential sex interactions. It is also uncertain whether adipokine derangements precede pulmonary disease or are a consequence of it. Future research will determine whether modulation of adipokines, independent of BMI, may allow novel ways to prevent or treat inflammatory pulmonary conditions.