Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics

Lensmar, C.; Nord, Magnus; Gudmundsson, G. H.; Roquet, A.; Andersson, Olof; Jörnvall, Hans; Eklúnd, Anders; Grünewald, Johan; Agerberth, Birgitta

doi:10.1007/pl00000738

Cited by 38 publications

(29 citation statements)

References 23 publications

(25 reference statements)

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“…Furthermore, our subjects were treated with only low to moderate doses of ICS, which also could explain why no inhibiting effect was seen on the increase in CC16 plasma levels. In a previous study, repeated low dose allergen challenge over seven consecutive days led to decreased concentrations of CC16 in BAL of subjects with allergic asthma (Lensmar et al 2000). In our study, CC16 levels in BAL were increased in single responders only, while the dual responders had significantly higher levels already at baseline.…”

Section: Discussionsupporting

confidence: 48%

“…In our study, CC16 levels in BAL were increased in single responders only, while the dual responders had significantly higher levels already at baseline. The allergen exposure in our study was higher and the time of sampling was different compared to the study by Lensmar et al (Lensmar et al 2000), with our results reflecting more of an acute inflammatory response. The absence of an increase in CC16 levels in BAL among the dual responders could be due to some form of desensitization of their club cells, thus reducing the anti-inflammatory response and the capacity of released CC16 to inhibit the LAR.…”

Section: Discussioncontrasting

confidence: 42%

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Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

et al. 2017

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Section: Discussionsupporting

confidence: 48%

Section: Discussioncontrasting

confidence: 42%

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

et al. 2017

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“…SINGH and KATYAL [34] suggested that CC10 may function as a regulator of inflammation in the lung, a notion which is still a matter of debate [28,[52][53][54][55]. CC10 was reported to be decreased in various conditions of inflammation [53,56,57], and deficiency in CC10 as a result of transgenic experiments or in humans with a chronic CC10 deficiency, e.g. in long-term cigarette smokers [58,59], appears to be characterised by a tendency towards an exaggerated inflammatory response [53,55], and may contribute to carcinogenesis [59].…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cellsin vivo

Fehrenbach

Fehrenbach²,

Pan³

et al. 2002

Eur Respir J

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Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo. H. Fehrenbach, A. Fehrenbach, T. Pan, M. Kasper, R.J. Mason. #ERS Journals Ltd 2002. ABSTRACT: Keratinocyte growth factor (KGF) is a potent mitogen of pulmonary bronchial and alveolar epithelial cells. However, it is unclear which type(s) of airway epithelial cells (AEC) proliferate(s) in response to KGF.AEC proliferation was induced in rats by either endobronchial instillation of 5 mg recombinant human (rHu) KGF per kg body weight or by adenoviral transfer of the human KGF gene (Ad5-HuKGF). Alterations in terminal airway AEC were followed for up to 7 days after rHuKGF, and for up to 28 days after Ad5-HuKGF.Cell proliferation, as assessed by immunohistochemistry (IHC) for incorporated 5-bromo-29-deoxyuridine (BrdU) and quantified by stereology, peaked at days 1-2 and was resolved by day 7 after rHuKGF and by day 21 after Ad5-HuKGF. Double immunofluorescence labelling for BrdU or Ki-67 on the one hand, and for Clara cell specific protein 10 (CC10) and calcitonin-gene related peptide on the other hand, demonstrated that Clara cells, not pulmonary neuroendocrine cells, proliferated in response to human KGF. TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) method in conjunction with IHC for MNF116 failed to detect significant numbers of apoptotic AEC. IHC in conjunction with stereology revealed transient phenotypic alterations with a decrease in CC10, an increase in surfactant protein D and an increase in CD44v6 in AEC.The authors conclude that Clara cells responded to human keratinocyte growth factor in vivo by proliferation as well as by changes in protein expression, whereas no significant response was observed in pulmonary neuroendocrine cells. As Clara cells are intimately involved in airway epithelial repair, ion and fluid transport, and modulate lung inflammation, the potential of human keratinocyte growth factor to protect the lung may in part rely on the response of Clara cells.

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“…Impaired repair mechanisms in the human epithelium of the airway have also been demonstrated by the up-regulation of metalloproteinase-9 in extracellular matrix in arsenic-exposed subjects (36). Clara cell 16 protein, which is known to play an important role in protecting the alveolar epithelium of the lung in chronic inflammation (37,38), has also been impacted by arsenic exposure (27).…”

Section: Discussionmentioning

confidence: 99%

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

Parvez

Chen

Yunus

et al. 2013

Am J Respir Crit Care Med

112

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Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator-administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV 1 (246.5 ml; P , 0.0005) and FVC (253.1 ml; P , 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV 1 (248.3 ml; P , 0.005) and FVC (255.2 ml; P , 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV 1 (274.4 ml, P , 0.01; and 2116.1 ml, P , 0.05) and FVC (272.8 ml, P ¼ 0.02; and 2146.9 ml, P ¼ 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low-to moderate-dose range.Keywords: arsenic exposure; lung function; Bangladesh Arsenic from drinking water has been linked with cancers, dermatologic, cardiovascular, reproductive, and neurotoxic outcomes among adults and children (1-8). Chronic exposure to arsenic has also been linked to nonmalignant respiratory effects including respiratory symptoms, chronic obstructive pulmonary disease, and respiratory disease mortality (9-12). However, the evidence of the effect of arsenic exposure on lung function is limited, especially at the low-to moderate-dose ranges. Several studies from arsenic-endemic areas of South Asia reported lower FEV 1 and FVC among individuals with arsenical skin lesions or drinking water with very high levels of arsenic (.250 mg/L) (13-15). Interestingly, a recent retrospective study from Chile identified that those exposed to arsenic either in utero or early life had a lower FEV 1 (11.5%; P ¼ 0.04) and FVC (12.2%; P ¼ 0.04) in adulthood compared with those unexposed (16).The published studies measuring pulmonary function involved small sample sizes and most lacked individual-level exposure data or measured arseni...

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Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics

Cited by 38 publications

References 23 publications

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cellsin vivo

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

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