Genetic polymorphisms in the surfactant proteins in systemic sclerosis in Japanese: T/T genotype at 1580 C/T (Thr131Ile) in the SP-B gene reduces the risk of interstitial lung disease

Sumita, Yoshiko; Sugiura, Tomoko; Kawaguchi, Yasushi; Baba, Sayumi; Soejima, Makoto; Murakawa, Yohko; Hara, Masako; Kamatani, Naoyuki

doi:10.1093/rheumatology/kem355

Cited by 31 publications

(16 citation statements)

References 19 publications

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“…SP-BC/T1580 is functionally one of the most important (26,27). This SP-BC/T1580 polymorphism is not only associated with pneumonia and pneumonia-induced ARDS (21,28,29), but also with neonatal respiratory distress syndrome (RDS) (30), and interstitial lung disease (ILD) (31). The detailed mechanisms for the increased susceptibility of SP-B C allele to these pulmonary diseases are unknown (6,27,32).…”

Section: Resultsmentioning

confidence: 99%

Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

Abdel-Razek

et al. 2016

Shock

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Staphylococcus aureus is a common cause of nosocomial pneumonia frequently resulting in acute respiratory distress syndrome (ARDS). Surfactant protein B (SP-B) gene expresses two proteins involved in lowering surface tension and host defense. Genotyping studies demonstrate a significant association between human SP-B genetic variants and ARDS. Curcumins have been shown to attenuate host inflammation in many sepsis models. Our hypothesis is that functional differences of SP-B variants and treatment with curcumin (CMC2.24) modulate lung injury in bacterial pneumonia. Humanized transgenic mice, expressing either SP-B T or C allele without mouse SP-B gene, were used. Bioluminescent labeled S. aureus Xen36 (50 μl) was injected intratracheally to cause pneumonia. Infected mice received daily CMC2.24 (40 mg/kg) or vehicle alone by oral gavage. Dynamic changes of bacteria were monitored using in vivo imaging system. Histological, cellular and molecular indices of lung injury were studied in infected mice 48h after infection. In vivo imaging analysis revealed total flux (bacterial number) was higher in the lung of infected SP-B-C mice compared to infected SP-B-T mice (p<0.05). Infected SP-B-C mice demonstrated increased mortality, lung injury, apoptosis and NF-κB expression compared to infected SP-B-T mice. Compared to controls, CMC2.24 treatment significantly reduced the following: mortality, total bacterial flux and lung tissue apoptosis, inflammatory cells, NF-κB expression (p<0.05), and MMPs-2, -9, -12 activities (p<0.05). We conclude that mice with SP-B-C allele are more susceptible to S. aureus pneumonia than mice with SP-B-T allele; and that CMC2.24 attenuates lung injury thus reducing mortality.

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Section: Resultsmentioning

confidence: 99%

Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

Abdel-Razek

et al. 2016

Shock

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“…The SNP (rs11130866 C/T) studied in the present work has been found to be associated with several pulmonary diseases in several independent groups [13] [7,12]. For instance, individual with C/C genotype was found more susceptible to RDS [29] while individual with T/T genotype was found to protect the patients with SSC against the development of ILD[7].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, individual with C/C genotype was found more susceptible to RDS [29] while individual with T/T genotype was found to protect the patients with SSC against the development of ILD[7]. The individuals carrying one or more C allele had more severe lung injury and required MV compared to those with T/T genotype [30].…”

Section: Discussionmentioning

confidence: 99%

“…hSP-B genetic variation is associated with various lung diseases, like respiratory distress syndrome in pre-term neonates (RDS), congenital alveolar protein deposition disease (CAP), bronchopulmonary dysplasia (BPD) [6], and the interstitial lung disease [7]. Critical mutations of hSP-B gene result in SP-B deficiency which is lethal for newborn infants [8].…”

Section: Introductionmentioning

confidence: 99%

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Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia

Chen

et al. 2016

Biochemical and Biophysical Research Communications

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Surfactant protein B (SP-B) is essential for lung function. Previous studies have indicated that a SP-B 1580C/T polymorphism (SNP rs1130866) was associated with lung diseases including pneumonia. The SNP causes an altered N-linked glycosylation modification at Asn129 of proSP-B, e.g. the C allele with this glycosylation site but not in the T allele. This study aimed to generate humanized SP-B transgenic mice carrying either SP-B C or T allele without a mouse SP-B background and then examine functional susceptibility to bacterial pneumonia in vivo. A total of 18 transgenic mouse founders were generated by the DNA microinjection method. These founders were back-crossed with SP-B KO mice to eliminate mouse SP-B background. Four founder lines expressing similar SP-B levels to human lung were chosen for further investigation. After intratracheal infection with 50μl of P. aeruginosa solution (1×107 CFU/mouse) or saline in SP-B-C, SP-B-T mice the mice were sacrificed 24 hours post-infection and tissues were harvested. Analysis of surfactant activity revealed differential susceptibility between SP-B-C and SP-B-T mice to bacterial infection, e.g. higher minimum surface tension in infected SP-B-C versus infected SP-B-T mice. These results demonstrate for the first time that human SP-B C allele is more susceptible to bacterial pneumonia than SP-B T allele in vivo.

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“…Results of another study have shown the incidence of SP-B deficiency in African Americans to be higher than in Caucasian Americans (12). The SP-B gene mutation has been shown to be associated with some respiratory diseases, including neonatal RDS, acute respiratory distress syndrome, congenital pulmonary alveolar proteinosis, adult chronic obstructive pulmonary emphysema and chronic lung diseases in children (13–15). …”

Section: Discussionmentioning

confidence: 99%

Correlation between surfactant protein B mRNA expression and neonatal respiratory distress syndrome

Yin

Fan

et al. 2012

Experimental and Therapeutic Medicine

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The aim of this study was to investigate whether surfactant-associated protein B (SP-B) mRNA deficiency is involved in the pathogenesis of neonatal respiratory distress syndrome (RDS). A total of 60 unrelated neonates who died of RDS were recruited as the RDS group and subgrouped into a ≤32-, a 32–36+6- and a ≥37-week group (n=20 per group) on the basis of gestational age. In addition, 60 neonates who succumbed to other diseases were enrolled as controls. The lung tissues were collected within 30 min after death. In situ hybridization was conducted to detect SP-B mRNA expression in the lung. The frequency of SP-B mRNA deficiency was also calculated. Among the RDS groups, the SP-B mRNA levels were significantly higher compared to those in the control group (t=7.812, P<0.001), but were comparable among RDS patients with different gestational ages (F=2.348, P>0.105). Among the control groups, the SP-B mRNA levels increased with the increase in gestational age (F=50.124, P<0.001). In the ≤32-week group, the number of cells positive for SP-B mRNA in RDS patients was markedly reduced as compared to that of the controls (t=3.185, P<0.01). In the 32–36+6-week group, the number of cells positive for SP-B mRNA in RDS patients was significantly smaller compared to that of the controls (t=9.342, P<0.001). In the ≥37-week group, the number of cells positive for SP-B mRNA in RDS patients was markedly smaller compared to that in the controls (t=4.238, P<0.001). Among RDS neonates, SP-B mRNA deficiency was noted in 35 patients with a frequency of 58.3%. In the control group, SP-B mRNA deficiency was noted in 8 patients with a frequency of 13.3%, which was markedly lower compared to that in the RDS group (χ2=26.421, P<0.001). The results of the present study therefore suggest that SP-B mRNA deficiency is involved in the pathogenesis of RDS.

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Genetic polymorphisms in the surfactant proteins in systemic sclerosis in Japanese: T/T genotype at 1580 C/T (Thr131Ile) in the SP-B gene reduces the risk of interstitial lung disease

Abstract: In SSc, where massive fibrosis occurs, possession of the T/T genotype in the SP-B gene would reduce the risk of ILD in Japanese.

Cited by 31 publications

References 19 publications

Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia

Correlation between surfactant protein B mRNA expression and neonatal respiratory distress syndrome

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