Multifunctional Role of Human SPLUNC1 in Pseudomonas aeruginosa Infection

Sayeed, Sameera; Nistico, Laura; Croix, Claudette St.; Di, Y. Peter

doi:10.1128/iai.00500-12

Cited by 50 publications

(81 citation statements)

References 37 publications

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“…These TG mice exhibited more enhanced antibacterial activity than their WT littermates (23). We also recently reported that recombinant human SPLUNC1 protein (rSPLUNC1) displayed chemotactic properties in recruiting neutrophils and macrophages in vitro (25). To explore whether this chemotactic function is relevant in a more biological setting, we examined the effects of SPLUNC1 overexpression in modulating the host response to SWCNTs in vivo, using the established TG animal model.…”

Section: Enhanced Leukocyte Recruitment In Splunc1 Tg Micementioning

confidence: 99%

“…SPLUNC1 exerts antimicrobial activity, and mice overexpressing SPLUNC1 exhibit enhanced protection against Pseudomonas aeruginosa and Mycoplasma pneumoniae (23,24). SPLUNC1 has also been reported to bind the Gram-negative bacteria cell wall component LPS (25,26). Moreover, SPLUNC1 may be required to regulate certain physical properties of airway surface liquid that are critical for proper mucociliary clearance in the lung, including airway surface liquid volume (27,28) and surface tension (29)(30)(31).…”

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confidence: 99%

“…Moreover, SPLUNC1 may be required to regulate certain physical properties of airway surface liquid that are critical for proper mucociliary clearance in the lung, including airway surface liquid volume (27,28) and surface tension (29)(30)(31). We recently demonstrated that SPLUNC1 exhibits a chemotactic property that recruits leukocytes in helping with the clearance of bacteria (25). Although the protective functions of SPLUNC1 are likely realized through several, if not all, of these mechanisms, experimental analyses of the specific pathways involved in the responses to microbial pathogens are obscured by the multiplicity of possible targets.…”

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confidence: 99%

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Dual Acute Proinflammatory and Antifibrotic Pulmonary Effects of Short Palate, Lung, and Nasal Epithelium Clone–1 after Exposure to Carbon Nanotubes

Tkach

Yanamala

et al. 2013

Am J Respir Cell Mol Biol

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Carbon nanotubes (CNTs; allotropes of carbon with a cylindrical nanostructure) have emerged as one of the most commonly used types of nanomaterials, with numerous applications in industry and biomedicine. However, the inhalation of CNTs has been shown to elicit pulmonary toxicity, accompanied by a robust inflammatory response with an early-onset fibrotic phase. Epithelial host-defense proteins represent an important component of the pulmonary innate immune response to foreign inhalants such as particles and bacteria. The short palate, lung, and nasal epithelium clone-1 (SPLUNC1) protein, a member of the bactericidal/permeability-increasing-fold (BPIF)-containing protein family, is a 25-kD secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been shown to have multiple functions, including antimicrobial and chemotactic activities, as well as surfactant properties. This study sought to assess the importance of SPLUNC1-mediated pulmonary responses in airway epithelial secretions, and to explore the biological relevance of SPLUNC1 to inhaled particles in a single-walled carbon nanotube (SWCNT) model. Using Scgb1a1-hSPLUNC1 transgenic mice, we observed that SPLUNC1 significantly modified host inflammatory responses by increasing leukocyte recruitment and enhancing phagocytic activity. Furthermore, we found that transgenic mice were more susceptible to SWCNT exposure at the acute phase, but showed resistance against lung fibrogenesis through pathological changes in the long term. The binding of SPLUNC1 also attenuated SWCNT-induced TNF-a secretion by RAW 264.7 macrophages. Taken together, our data indicate that SPLUNC1 is an important component of mucosal innate immune defense against pulmonary inhaled particles.Keywords: SPLUNC1; BPIFA1; carbon nanotube; fibrosis; inflammationThe advancement of nanotechnology presents many opportunities and benefits for new materials with significantly improved properties, as well as revolutionary applications in the fields, for example, of electronics, energy, environment, biomaterials, and medicine (1). Single-walled carbon nanotubes (SWCNTs; allotropes of carbon with a cylindrical nanostructure) have emerged as one of the most commonly used types of nanomaterials, with numerous applications in industry and biomedicine. SWCNTs have a diameter of only approximately 1 nanometer, but their length can be more than a million times greater. Although SWCNTs are versatile and beneficial in various applications, the inhalation of these nanoparticles exerts negative effects on the normal physiological functions of lungs, and causes pulmonary toxicity (2-5). We previously demonstrated that the pharyngeal aspiration of SWCNTs elicits pulmonary effects in C57BL/6 mice, with a combination of robust, acute inflammation and early-onset yet progressive fibrosis and granulomas (2, 5, 6). The early phase of lung innate immune responses to SWCNTs is characterized by inflammation mediated by phagocytic cells, namely, polymorphonuclear leukocytes (PMNs) and alveolar m...

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Section: Enhanced Leukocyte Recruitment In Splunc1 Tg Micementioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Dual Acute Proinflammatory and Antifibrotic Pulmonary Effects of Short Palate, Lung, and Nasal Epithelium Clone–1 after Exposure to Carbon Nanotubes

Tkach

Yanamala

et al. 2013

Am J Respir Cell Mol Biol

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“…A number of previous studies have demonstrated that BPIFA1 is involved in various physiological and pathological processes (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). It is considered to be involved in inflammatory responses to irritants in the upper airway (2-7).…”

Section: Introductionmentioning

confidence: 99%

Increased expression of BPI fold-containing family A member 1 is associated with metastasis and poor prognosis in human colorectal carcinoma

Wang

Jiang

et al. 2017

Oncology Letters

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Abstract. Bactericidal or permeability-increasing protein fold-containing family A member 1 (BPIFA1) has been demonstrated to be involved in inflammatory responses in the upper airway and the progression of non-small cell lung cancer. However, the expression levels of BPIFA1 and its clinical prognostic significance in colorectal carcinoma (CRC) has not yet been elucidated. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression levels of BPIFA1 in CRC and normal mucosal tissues. The associations between BPIFA1 expression levels and clinicopathological characteristics, and its predictive value for prognosis in CRC, were statistically evaluated as appropriate. The expression levels of BPIFA1 were revealed to be upregulated at the transcriptional and translational levels in CRC tissues, compared with in normal mucosal tissues. A high expression level of BPIFA1 is significantly associated with invasion depth (P=0.040), lymph node metastasis (P=0.035) and distant metastasis (P=0.010). Furthermore, Kaplan-Meier analysis indicated that BIPFA1 overexpression is associated with short survival time, and the Cox proportional hazards model of risk analysis indicated that BPIFA1 is an independent prognostic factor for patients with CRC. The results of the present study suggested that BPIFA1 expression is upregulated in CRC tissues, and that an increased expression level of BPIFA1 is associated with tumor invasion, metastasis and poor prognosis, indicating that BPIFA1 may be a potential clinical prognostic predictor and therapeutic target for patients with CRC. IntroductionColorectal carcinoma (CRC) is the one of the most common types of cancer, and is the fifth leading cause of cancer-associated mortalities worldwide (1). Despite recent advancements in the surgical techniques, radiotherapy and chemotherapy available to patients diagnosed with CRC over the past several decades, the overall survival rate has not significantly improved. The existence of numerous known carcinogens and varying genetic backgrounds makes it difficult to determine which factors are most important in the development of CRC. Thus, there is a requirement to further understand the underlying molecular mechanisms and identify novel prognostic biomarkers and therapeutic targets to provide improved treatment strategies for CRC.Bactericidal or permeability-increasing protein fold-containing family A member 1 (BPIFA1) is a protein-coding gene specifically expressed in the upper airways and nasopharyngeal regions. A number of previous studies have demonstrated that BPIFA1 is involved in various physiological and pathological processes (2-19). It is considered to be involved in inflammatory responses to irritants in the upper airway (2-7). BPIFA1 may decrease mycoplasma pneumonia expression levels and inhibit interleukin 8 (8). BPIFA1 protein was also revealed to have antibacterial activity against gram-negative bacteria (9,10). The anti-inflammatory function has been associated with the regulation of macro...

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“…[4][5][6] Normally, LunX protein expression is relatively low in healthy individuals and only up-regulated in upper respiratory tract upon infection by pathogenic microbes. 7 We recently showed that LunX is overexpressed in the majority of a large panel of NSCLCs and is higher in lymph node metastases. However, similar results were rarely detected in benign lung disease and other organs (colon, liver and breast).…”

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confidence: 99%