Club cell secretory protein (CC16) in gastric fluid at birth and subsequent lung disease in preterm infants

Hagman, Cecilia; Björklund, Lars; Hellgren, Gunnel; Tufvesson, Ellen; Hansen‐Pupp, Ingrid

doi:10.1002/ppul.24128

Cited by 6 publications

(8 citation statements)

References 31 publications

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“…Club cell protein (CC16), a secretory protein found at extremely high levels in the lungs, is widely believed to be of great significance in anti-inflammatory and antioxidant stress [8, 9]. Studies performed to understand the roles of CC16 have revealed that recombinant CC16 (rCC16) not only shows therapeutic effects in disease models but also helps mitigate the respiratory function of premature infants and newborn lambs [10–12].…”

Section: Introductionmentioning

confidence: 99%

Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis

Zhou

Yang

et al. 2019

J Neuroinflammation

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BackgroundSepsis is a critical disease associated with extremely high mortality. Some severe forms of sepsis can induce brain injury, thus causing behavioral and cognitive dysfunction. Pyroptosis is a type of cell death that differs from apoptosis and plays an important role in the occurrence and development of infectious diseases, nervous system-related diseases. A recent study has found that there is pyroptosis in the hippocampus of sepsis-induced brain injury, but its mechanism and treatment scheme have not been evaluated.MethodsWe established immediately a septic rat model by cecal ligation and perforation (CLP) after administration with recombinant club cell protein (rCC16) and/or U46619 in different groups. The clinical performance, survival percentage, vital signs, and neurobehavioral scores were monitored at different time points. Cortical pathological changes were also examined. The expression of cortical nucleotide-binding domain leucine-rich repeat-containing pyrin domain-containing 3 (NLRP3), caspase-1, (p)-p38 mitogen-activated protein kinase (MAPK), and (p)-extracellular signal-related kinase (ERK) was detected by western blotting and immunofluorescence analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha in the cortical supernatant were detected by enzyme-linked immunosorbent assay.ResultsCompared with the sham group, the clinical performance, survival percentage, vital signs, and severe cortical pathological changes in the CLP group were worse; NLRP3, caspase-1, and inflammatory factor levels were increased; and phosphorylation of p38 MAPK and ERK was also increased. Meanwhile, multiple indicators were deteriorated further after administration of U46619 in CLP rats. The clinical performance of CLP rats, however, was better after rCC16 administration; cortical pathological changes were attenuated; and NLRP3, caspase-1, and inflammatory factor levels and the phosphorylation of signaling pathway proteins (p38 MAPK and ERK) were reduced. Interestingly, the CLP rats showed the opposite changes in all indicators after administration with both rCC16 and U46619 when compared with those administered rCC16 alone.ConclusionsIn sepsis, rCC16 inhibits cortical pyroptosis through p38 MAPK and ERK signaling pathways. Meanwhile, rCC16 has a protective effect on newborn rats with sepsis, but it is not clear whether its mechanism is directly related to pyroptosis.

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Section: Introductionmentioning

confidence: 99%

Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis

Zhou

Yang

et al. 2019

J Neuroinflammation

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“…Another study documented that OVA-challenged CC16 −/− mice exhibited more severe airway dysfunction than wild mice [26]. Also, a low concentration of CC16 in gastric uid at birth was thought to be correlated with increased lung in ammation in the neonatal period [27].Thus, on the basis of detailed prior studies of the role of CC16 in airway diseases, we postulated that supplementary CC16 may restore airway in ammation in HDM-induced asthma. In the current study, by the establishment of an experimental model of murine asthma, our results demonstrated that exogenous administration of CC16 decreased in ammatory cells counts and Th2 cytokines levels including IL-4, IL-5, IL-13 as well as HDM-speci c IgE in the BALF of asthmatic mice.…”

Section: Discussionmentioning

confidence: 91%

Clara Cell 16KDa Protein Mitigates House Dust Mite-Induced Airway Inflammation and Damage via Regulating Airway Epithelial Cell Apoptosis in a Manner Dependent on HMGB1-Mediated Signaling Inhibition.

Liu

Zhang

et al. 2020

Preprint

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Background: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16.Methods: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5ug/g or 10ug/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection.Results: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis.Conclusions: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential therapeutic option for HDM-induced asthma.

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“…Not only markers of injury, but maladaptive decrements of protective factors may portend BPD. Hagman and colleagues correlated gastric concentrations of club cell secretory protein 16 (CC16, previously termed CC10, CCSP, the gene product of SCTGB1A1 ) with evidence of lung inflammation at birth and the risk to require higher respiratory support . A protective role against inflammation has long been ascribed to this protein, so it might be expected that low lung production—inferred from gastric contents that are largely amniotic fluid and hence in contact with the fetal lung—may represent impaired lung development or reduced anti‐inflammatory capacity.…”

Section: The Canary In the Coal Shaft: The Hunt For Early Markersmentioning

confidence: 99%

“…Hagman and colleagues correlated gastric concentrations of club cell secretory protein 16 (CC16, previously termed CC10, CCSP, the gene product of SCTGB1A1) with evidence of lung inflammation at birth and the risk to require higher respiratory support. 19 A protective role against inflammation has long been ascribed to this protein, so it might be expected that low lung production-inferred from gastric contents that are largely amniotic fluid and hence in contact with the fetal lung-may represent impaired lung development or reduced anti-inflammatory capacity. The authors found that gastric fluid and tracheal aspirate concentrations of CC16 correlated poorly, possibly due in part to small sample sizes but possibly attributable to dilution of the tracheal samples.…”

Section: The Canary In the Coal Shaft: The Hunt For Early Markersmentioning

confidence: 99%

2018 year in review: Part 2 of 4: Neonatal lung disease

Auten

2019

Pediatric Pulmonology

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Club cell secretory protein (CC16) in gastric fluid at birth and subsequent lung disease in preterm infants

Abstract: A low CC16 concentration in gastric fluid at birth was associated with increased inflammation in the trachea within the first 24 h of life and with more need for respiratory support in the neonatal period.

Cited by 6 publications

References 31 publications

Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis

Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis

Clara Cell 16KDa Protein Mitigates House Dust Mite-Induced Airway Inflammation and Damage via Regulating Airway Epithelial Cell Apoptosis in a Manner Dependent on HMGB1-Mediated Signaling Inhibition.

2018 year in review: Part 2 of 4: Neonatal lung disease

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