Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma

Lee, Tae-Hyeong; Jang, An‐Soo; Park, Jong‐Sook; Kim, Tae-Hoon; Choi, Young Kil; Shin, Hye-Rim; Park, Sung Woo; Uh, Soo‐Taek; Choi, Ji‐Yeob; Kim, Young Hoon; Kim, Yong-Bae; Kim, Sungryul; Chung, Il Yup; Jeong, Sung Hwan; Park, Choon-Sik

doi:10.1016/j.anai.2013.06.028

Cited by 73 publications

(62 citation statements)

References 38 publications

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“…Finally, we showed that BPIFB1 is localized to regions of goblet cell metaplasia. In addition to our previous proteomic study of COPD patients (24), elevated levels of BPIFB1 have been discovered in proteomic screening for other respiratory diseases, such as in the lung tissue of patients with cystic fibrosis (8), in sputum from patients with severe uncontrolled asthma (18), and in BALF from asthma patients after segmental allergen challenge (39). It is likely that sputum BPIFB1 levels reflect the homeostasis of the respiratory epithelium and may be upregulated in COPD as a result of smoking, chronic infection, and enhanced immune responses.…”

Section: Discussionmentioning

confidence: 99%

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing foldcontaining protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n ϭ 31), smokers (n ϭ 169), and patients with COPD (n ϭ 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV 1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smokingrelated lung diseases.

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Section: Discussionmentioning

confidence: 99%

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…S100A8 and S100A9 have recently been implicated in the pathogenesis of asthma, although their roles are unclear [5,13,15]. The expression of S100A9 in peripheral blood mononuclear cells is elevated during asthma exacerbations [16], and sputum levels of S100A9 were increased in patients with severe neutrophilic asthma [8]. Based on these findings, we aimed to further elucidate the associations and roles of S100A8 and S100A9 proteins in innate immune responses in the pathogenesis of baker's asthma.…”

Section: Discussionmentioning

confidence: 99%

“…S100A8 and S100A9 have long been considered biomarkers for several inflammatory diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, and inflammatory bowel disease [7]. Lee et al [8] have recently found a greater S100A9 protein expression in sputum neutrophils of uncontrolled severe asthma patients compared to controlled asthmatics. Moreover, S100A8 and S100A9 can activate human airway epithelial cells to induce the production of mucin 5AC [6], a glycoprotein highly secreted from asthmatic airway epithelium [9,10].…”

Section: Introductionmentioning

confidence: 99%

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Pham

Yoon

Ban

et al. 2015

Int Arch Allergy Immunol

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Background: S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. Methods: Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027A→G and -1608T→C were genotyped. Results: Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). Conclusion: S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.

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“…Recently, Kang et al [61] found that S100A9 protein stimulates human bronchial epithelial cells to induce MUC5AC protein, which is the main mucin protein in asthmatic airways, via TLR4 activation. A previous proteomic study of ours [62] demonstrates increased levels of S100A9 in sputum of neutrophilic patients with uncontrolled severe asthma compared to those with controlled asthma (Fig. 2).…”

Section: S100a9 In Neutrophilic Asthmamentioning

confidence: 55%

“…* p < 0.01 vs. neutrophilic subtypes of severe uncontrolled asthma. Adapted from Lee TH, et al Ann Allergy Asthma Immunol 2013;111:268-275.e1, with permission of Elsevier B. V. [62]. …”

Section: Figmentioning

confidence: 99%

Role of inflammasome activation in development and exacerbation of asthma

Lee

Song

Park

2014

Asia Pacific Allergy

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Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.

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Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma

Cited by 73 publications

References 38 publications

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Role of inflammasome activation in development and exacerbation of asthma

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