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Differential localisation of BPIFA1 (SPLUNC1) and BPIFB1 (LPLUNC1) in the nasal and oral cavities of mice.

ABSTRACT: Despite being initially identified in mice, little is known about the sites of production of members of the BPI fold (BPIF) containing (PLUNC) family of putative innate defence proteins in this species. These proteins have largely been considered to be specificaly expressed in the respiratory tract, and we have recently shown that they exhibit differential expression in the epithelium of the proximal airways. In this study, we have used species-specific antibodies to systematically localize two members of this protein family; BPIFA1 (PLUNC/SPLUNC1) and BPIFB1 (LPLUNC1) in adult mice. In general, these proteins exhibit distinct and only partially overlapping localization. BPIFA1 is highly expressed in the respiratory epithelium and Bowman's glands of the nasal passages, whereas BPIFB1 is present in small subset of goblet cells in the nasal passage and pharynx. BPIFB1 is also present in the serous glands in the proximal tongue where is co-localised with the salivary gland specific family member, BPIFA2E (parotid secretory protein) and also in glands of the soft palate. Both proteins exhibit limited expression outside of these regions. These results are consistent with the localization of the proteins seen in man. Knowledge of the complex expression patterns of BPIF proteins in these regions will allow the use of tractable mouse models of disease to dissect their function.

SUBMITTER: Musa M

PROVIDER: S-EPMC3505551 | biostudies-literature |

REPOSITORIES: biostudies-literature

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BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease.

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| S-EPMC3470695 | biostudies-literature

BPIFB1 (LPLUNC1) inhibits radioresistance in nasopharyngeal carcinoma by inhibiting VTN expression.

Project description:Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1, previously named LPLUNC1) is highly expressed in the nasopharynx and significantly downregulated in nasopharyngeal carcinoma (NPC). Low expression is also associated with poor prognosis in patients with NPC. Radiotherapy is a routine treatment for NPC; however, radioresistance is a major cause of treatment failure. Thus, we aimed to investigate the role of BPIFB1 in the radioresponse of NPC. Colony formation and cell survival results showed that BPIFB1 sensitized NPC cells to ionizing radiation. VTN, a previously identified BPIFB1-binding protein, was shown to induce cell proliferation and survival, G2/M phase arrest, DNA repair, activation of the ATM-Chk2 and ATR-Chk1 pathways, and anti-apoptotic effects after exposure to radiation, facilitating NPC cell radioresistance. However, BPIFB1 inhibited this VTN-mediated radioresistance, ultimately improving NPC radiosensitivity. In conclusion, this study is the first to demonstrate the functions of BPIFB1 and VTN in the NPC radioresponse. Our findings indicated that promoting BPIFB1 expression and targeting VTN might represent new therapeutic strategies for NPC.

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Association of innate defense proteins BPIFA1 and BPIFB1 with disease severity in COPD.

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BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM.

Project description:BackgroundBactericidal/Permeability-increasing-fold-containing family B member 1 (BPIFB1, previously termed LPLUNC1) is highly expressed in the nasopharynx, significantly downregulated in nasopharyngeal carcinoma (NPC), and associated with prognosis in NPC patients. Because metastasis represents the primary cause of NPC-related death, we explored the role of BPIFB1 in NPC migration and invasion.MethodsThe role of BPIFB1 in NPC metastasis was investigated in vitro and in vivo. A co-immunoprecipitation assay coupled with mass spectrometry was used to identify BPIFB1-binding proteins. Additionally, western blotting, immunofluorescence, and immunohistochemistry allowed assessment of the molecular mechanisms associated with BPIFB1-specific metastatic inhibition via vitronectin (VTN) and vimentin (VIM) interactions.ResultsOur results showed that BPIFB1 expression markedly inhibited NPC cell migration, invasion, and lung-metastatic abilities. Additionally, identification of two BPIFB1-interacting proteins, VTN and VIM, showed that BPIFB1 reduced VTN expression and the formation of a VTN-integrin αV complex in NPC cells, leading to inhibition of the FAK/Src/ERK signalling pathway. Moreover, BPIFB1 attenuated NPC cell migration and invasion by inhibiting VTN- or VIM-induced epithelial-mesenchymal transition.ConclusionsThis study represents the first demonstration of BPIFB1 function in NPC migration, invasion, and lung metastasis. Our findings indicate that re-expression of BPIFB1 might represent a useful strategy for preventing and treating NPC.

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The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium.

Project description:Bacterial permeability family member A1 (BPIFA1), also known as short palate, lung, and nasal epithelium clone 1 (SPLUNC1), is a protein involved in the antiinflammatory response. The goal of this study was to determine whether BPIFA1 expression in asthmatic airways is regulated by genetic variations, altering epithelial responses to type 2 cytokines (e.g., IL-13). Nasal epithelial cells from patients with mild to severe asthma were collected from the National Heart, Lung, and Blood Institute Severe Asthma Research Program centers, genotyped for rs750064, and measured for BPIFA1. To determine the function of rs750064, cells were cultured at air-liquid interface and treated with IL-13 with or without recombinant human BPIFA1 (rhBPIFA1). Noncultured nasal cells with the rs750064 CC genotype had significantly less BPIFA1 mRNA expression than the CT and TT genotypes. Cultured CC versus CT and TT cells without stimulation maintained less BPIFA1 expression. With IL-13 treatment, CC genotype cells secreted more eotaxin-3 than CT and TT genotype cells. Also, rhBPIFA1 reduced IL-13-mediated eotaxin-3. BPIFA1 mRNA levels negatively correlated with serum IgE and fractional exhaled nitric oxide. Baseline FEV1% levels were lower in the asthma patients with the CC genotype (n = 1,016). Our data suggest that less BPIFA1 in asthma patients with the CC allele may predispose them to greater eosinophilic inflammation, which could be attenuated by rhBPIFA1 protein therapy.

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Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

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| S-EPMC4450743 | biostudies-literature

Interleukin-13 Inhibits Lipopolysaccharide-Induced BPIFA1 Expression in Nasal Epithelial Cells.

Project description:Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP.

| S-EPMC4672888 | biostudies-literature

Survival analysis of 8785 malignant lymphoma cases in the oral and nasal cavities in the USA: a cohort study.

Project description:ObjectiveTo identify the factors associated with the survival of malignant Hodgkin and non-Hodgkin lymphomas in oral and nasal cavities.Study design. Retrospective cohort survival analysis.MethodsThe Surveillance, Epidemiology and End Results 18 database was used to analyse the factors associated with the 5-year survival rate of malignant lymphomas diagnosed in the oral cavity and pharynx (OCP) and nasal cavity and sinus (NCS) regions from 1988 to 2011 for all patients in the USA. Multivariable Cox regression models were used to calculate the HR of malignant lymphoma death overall and by the site of cancer diagnosis.ResultsAmong the 8785 patients included in the analysis, 4103 (46.7%) were women, 6096 (69.4%) were non-Hispanic (NH) white, 635 (7.2%) were NH black and 1209 (13.8%) were Hispanic patients of all races. We found that a higher 5-year survival rate of malignant lymphoma is associated with: female gender; younger age at diagnosis; NH white race/ethnicity; diagnosis in the oral cavity; receiving surgery/radiation and surgery/radiation, surgery and chemotherapy as the treatment; diagnosis at a localised stage and diagnosis in later calendar years. No association with lymphoma subtype was observed.ConclusionWe have identified several demographics and prognosis factors associated with the 5-year survival rate of malignant lymphomas in the OCP and NCS regions. These findings warrant greater public health attention on the prognosis of malignant lymphomas in the OCP and NCS regions among the most vulnerable populations.

| S-EPMC8679073 | biostudies-literature

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