scholarly journals IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection

2021 ◽  
Vol 4 (8) ◽  
pp. e202001000
Author(s):  
Alistair L Chenery ◽  
Silvia Rosini ◽  
James E Parkinson ◽  
Jesuthas Ajendra ◽  
Jeremy A Herrera ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Stress Responses ◽  
Tissue Injury ◽  
Critical Role ◽  
Surfactant Protein ◽  
Lung Damage ◽  
Surfactant Protein D ◽  
Nippostrongylus Brasiliensis ◽  
Pathway Analyses

IL-13 is implicated in effective repair after acute lung injury and the pathogenesis of chronic diseases such as allergic asthma. Both these processes involve matrix remodelling, but understanding the specific contribution of IL-13 has been challenging because IL-13 shares receptors and signalling pathways with IL-4. Here, we used Nippostrongylus brasiliensis infection as a model of acute lung damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. We found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung, and through proteomic and transcriptomic profiling, identified IL-13-dependent changes in matrix and associated regulators. We further showed a requirement for IL-13 in the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 induced cellular stress responses and regulated lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, in the context of acute lung damage, IL-13 has tissue-protective functions and regulates epithelial cell responses during type 2 immunity.

scholarly journals IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection

2020 ◽  
Author(s):  
AL Chenery ◽  
S Rosini ◽  
JE Parkinson ◽  
JA Herrera ◽  
Craig Lawless ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Stress Responses ◽  
Tissue Injury ◽  
Critical Role ◽  
Lung Damage ◽  
Surfactant Protein D ◽  
Nippostrongylus Brasiliensis ◽  
Tissue Remodelling

AbstractIL-13 plays a key role during protective type 2 immune responses at mucosal sites, such as during infection with nematodes. However, dysregulation of IL-13 can also contribute to the pathogenesis of atopic and fibrotic diseases such as allergic asthma. Matrix remodelling is an important component of repair processes in the lung but also a hallmark of chronic conditions involving fibrosis. Hence, understanding the role of IL-13 in tissue remodelling has important clinical implications. Since IL-13 shares receptors and signalling pathways with IL-4, disentangling the relative contributions of these type 2 cytokines has been challenging. Additionally, little is known about the singular role of IL-13 following acute tissue injury. In this study, we used Nippostrongylus brasiliensis infection as a model of acute lung tissue damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. Importantly, we found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung following infection. Through proteomic and transcriptomic profiling, we identified IL-13-dependent changes in matrix and associated regulators. We further showed that IL-13 is required for the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 was heavily involved in the induction of cellular stress responses and regulation of lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, we propose that IL-13 has tissue-protective functions during lung injury and regulates epithelial cell responses during type 2 immunity in this acute setting.

GATA6 regulates differentiation of distal lung epithelium

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2233-2246 ◽  
Author(s):  
Honghua Yang ◽  
Min Min Lu ◽  
Lili Zhang ◽  
Jeffrey A. Whitsett ◽  
Edward E. Morrisey
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Surfactant Protein ◽  
Gata Factor ◽  
Lung Epithelium ◽  
Alveolar Epithelial ◽  
Distal Lung ◽  
Transgenic Embryos

GATA6 is a member of the GATA family of zinc-finger transcriptional regulators and is the only known GATA factor expressed in the distal epithelium of the lung during development. To define the role that GATA6 plays during lung epithelial cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein in the distal lung epithelium of transgenic mice. Transgenic embryos lacked detectable alveolar epithelial type 1 cells in the distal airway epithelium. These embryos also exhibited increased Foxp2 gene expression, suggesting a disruption in late alveolar epithelial differentiation. Alveolar epithelial type 2 cells, which are progenitors of alveolar epithelial type 1 cells, were correctly specified as shown by normal thyroid transcription factor 1 and surfactant protein A gene expression. However, attenuated endogenous surfactant protein C expression indicated that alveolar epithelial type 2 cell differentiation was perturbed in transgenic embryos. The number of proximal airway tubules is also reduced in these embryos, suggesting a role for GATA6 in regulating distal-proximal airway development. Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter. Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse.

Pulmonary dysfunction in neonatal SP-B-deficient mice

1997 ◽  
Vol 273 (4) ◽  
pp. L875-L882 ◽  
Author(s):  
Keisuke Tokieda ◽  
Jeffrey A. Whitsett ◽  
Jean C. Clark ◽  
Timothy E. Weaver ◽  
Kazushige Ikeda ◽  
...  
Keyword(s):  
Critical Role ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Phospholipid Content ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Lung Expansion ◽  
B Mice ◽  
Deficient Mice

Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/− mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/− mice, lung volumes and compliances were decreased markedly in homozygous SP-B−/− mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B−/− mice and was reduced in the SP-B+/− mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/− and SP-B−/− mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B−/− mice and in reduced lung compliance in SP-B+/+ and SP-B+/− mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

scholarly journals Critical role of amino acid position 343 of surfactant protein-D in the selective binding of glycolipids from Mycobacterium tuberculosis

Glycobiology ◽  
2009 ◽  
Vol 19 (12) ◽  
pp. 1473-1484 ◽  
Author(s):  
Tracy K Carlson ◽  
Jordi B Torrelles ◽  
Kelly Smith ◽  
Tim Horlacher ◽  
Riccardo Castelli ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Critical Role ◽  
Amino Acid Position ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Selective Binding

scholarly journals Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Raquel Arroyo ◽  
Paul S. Kingma
Keyword(s):  
Immune Response ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Tissue Injury ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Innate Immune ◽  
Surfactant Protein D

AbstractSurfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.

Surfactant protein D in chronic obstructive pulmonary disease and type 2 diabetes mellitus

2017 ◽  
Vol 30 (1) ◽  
pp. 297
Author(s):  
MaiA.H. Abou Elenin ◽  
NaglaaM Ghanayem ◽  
ElsayedS Abou Elnour ◽  
RababA El Wahsh ◽  
RaniaM.A. El-Shazlya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Obstructive Pulmonary Disease ◽  
Type 2 Diabetes Mellitus ◽  
Pulmonary Disease ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Serum surfactant protein D is a potential biomarker of lung damage in systemic sclerosis

2016 ◽  
Author(s):  
Riccardo Messina ◽  
Alida Benfante ◽  
Daniela Castiglia ◽  
Claudia I. Gruttad'Auria ◽  
Nicola Scichilone
Keyword(s):  
Systemic Sclerosis ◽  
Surfactant Protein ◽  
Lung Damage ◽  
Surfactant Protein D ◽  
Potential Biomarker

scholarly journals Serum Surfactant Protein D as a Biomarker for Measuring Lung Involvement in Obese Patients With Type 2 Diabetes

2017 ◽  
Vol 102 (11) ◽  
pp. 4109-4116 ◽  
Author(s):  
Carolina López-Cano ◽  
Albert Lecube ◽  
Marta García-Ramírez ◽  
Xavier Muñoz ◽  
Enric Sánchez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Obese Patients ◽  
Lung Involvement

scholarly journals Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

2014 ◽  
Vol 306 (9) ◽  
pp. L887-L895 ◽  
Author(s):  
Sofie L. Johansson ◽  
Qihua Tan ◽  
René Holst ◽  
Lene Christiansen ◽  
Niels C. G. Hansen ◽  
...  
Keyword(s):  
Lung Function ◽  
Single Nucleotide Polymorphisms ◽  
Tobacco Smoke ◽  
Tobacco Smoking ◽  
Surfactant Protein ◽  
Lung Damage ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Variation in surfactant protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The association between serum SP-D (sSP-D) and expiratory lung function was assessed in a cross-sectional design in a Danish twin population ( n = 1,512, 18–72 yr old). The adjusted heritability estimates for expiratory lung function, associations between SP-D gene ( SFTPD) single-nucleotide polymorphisms or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 s and forced vital capacity in the presence of current tobacco smoking but not in nonsmokers. The two SFTPD single-nucleotide polymorphisms, rs1923536 and rs721917, and haplotypes, including these single-nucleotide polymorphisms or rs2243539, were inversely associated with expiratory lung function in interaction with smoking. In conclusion, SP-D is phenotypically and genetically associated with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive pulmonary disease initiation and development.

Sign in / Sign up

Export Citation Format

Share Document