β-Defensin 1 Contributes to Pulmonary Innate Immunity in Mice

Moser, Christian; Weiner, Daniel J.; Лысенко, Елена; Bals, Robert; Weiser, Jeffrey N.; Wilson, James M.

doi:10.1128/iai.70.6.3068-3072.2002

Cited by 203 publications

(145 citation statements)

References 24 publications

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“…For example, previous studies using surfactant proteins A or D or ␤-defensin knockout mice have demonstrated impaired bacterial clearance from the lung. [27][28][29] In addition, airway epithelial cells produce several other major host defense molecules such as lactotransferrin. 30 The present results of impaired Mp clearance from SPLUNC1 Ϫ/Ϫ mouse lungs advance the lung innate immunity field by demonstrating the in vivo function of SPLUNC1.…”

Section: Discussionmentioning

confidence: 99%

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

Gally

Smith

et al. 2011

The American Journal of Pathology

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Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is highly expressed in normal airways, but is dramatically decreased in allergic and cigarette smoke exposure settings. We have previously demonstrated SPLUNC1 in vitro antibacterial property against Mycoplasma pneumoniae (Mp). However, its in vivo biological functions remain unclear. The objectives of this study were to determine the in vivo functions of SPLUNC1 following bacterial (eg, Mp) infection, and to examine the underlying mechanisms. We generated SPLUNC1-deficient mice and utilized transgenic mice overexpressing human SPLUNC1 exclusively within the airway epithelium. These mice were infected with Mp and, twenty-four hours post infection, their host defense responses were compared to littermate controls. Mp levels and inflammatory cells increased in the lungs of SPLUNC1 ؊/؊ mice as compared to wild type controls. SPLUNC1 deficiency was shown to contribute to impaired neutrophil activation. In contrast, mice overexpressing hSPLUNC1 exclusively in airway epithelial cells demonstrated lower Mp levels. Furthermore, neutrophil elastase activity was significantly increased in mice overexpressing hSPLUNC1. Lastly, we demonstrated that SPLUNC1 enhanced Mp-induced human neutrophil elastase (HNE) activity, and HNE directly inhibited the growth of Mp. Our findings demonstrate a critical in vivo role of SPLUNC1 in host defense against bacterial infection, and likely provide a novel therapeutic approach to restore impaired lung innate immune responses to bacteria in patients with chronic lung diseases.

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Section: Discussionmentioning

confidence: 99%

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

Gally

Smith

et al. 2011

The American Journal of Pathology

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“…18,19 Mice deficient in hBD-1 had delayed clearance of Haemophilus influenzae from the lung. 20 The DEFB1 sequence contains nuclear factor interleukin-6 and interferon-d consensus sites, suggesting that inflammatory markers induce hBD-1 expression. 21 In addition, complex interactions between serpins and defensin suggest that defensins also have a role in regulating inflammatory processes within the airway.…”

Section: Discussionmentioning

confidence: 99%

Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children

Leung

Liu

et al. 2006

Genes Immun

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Human b-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5 0 -untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5-18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles À20A and À52G (P ¼ 0.041-0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P ¼ 0.001) and for G-52A under both recessive and codominant models (P ¼ 0.008 and 0.035). The recessive model covariate was also positive and significant (P ¼ 0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05-2.57); P ¼ 0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.

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“…The key role of antimicrobial peptides in mammalian host defense is made evident by mice with disrupted antimicrobial peptide genes that are prone to infection in the affected epithelial organs, including the skin (3)(4)(5). In humans, the role of epithelial antimicrobial peptides in host defense is suggested by studies of two major human skin diseases with a defective skin barrier, atopic dermatitis and psoriasis.…”

Section: Differential Regulation Of ␤-Defensin Expression In Humanmentioning

confidence: 99%

Differential Regulation of β-Defensin Expression in Human Skin by Microbial Stimuli

Sørensen

Thapa

Rosenthal

et al. 2005

The Journal of Immunology

224

184

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In response to infection, epithelia mount an innate immune response that includes the production of antimicrobial peptides. However, the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia are not understood. We analyzed the molecular links between infection and the expression of three antimicrobial peptides of the β-defensin family, human β-defensin (hBD)-1, hBD-2, and hBD-3 in the human epidermis. After exposure to microbe-derived molecules, both monocytes and lymphocytes stimulated the epidermal expression of hBD-1, hBD-2, and hBD-3. The induced expression of hBD-3 was mediated by transactivation of the epidermal growth factor receptor. The mechanisms of induction of hBD-1 and hBD-3 were distinct from each other and from the IL-1-dependent induction of hBD-2 expression. Thus during inflammation, epidermal expression of β-defensins is mediated by at least three different mechanisms.

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β-Defensin 1 Contributes to Pulmonary Innate Immunity in Mice

Cited by 203 publications

References 24 publications

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

SPLUNC1 Promotes Lung Innate Defense Against Mycoplasma pneumoniae Infection in Mice

Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children

Differential Regulation of β-Defensin Expression in Human Skin by Microbial Stimuli

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