FK506-binding Protein 13 Expression is Upregulated in Interstitial Lung Disease and Correlated with Clinical Severity: A Potentially Protective Role

ABSTRACTPulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. Endoplasmic reticulum (ER) stress initiates the unfolded protein response (UPR), a cellular stress response pathway that has been implicated in both inflammatory and fibrotic processes. Here, we sought to investigate the role of the 13 kDa FK506-binding protein (FKBP13), an ER stress-inducible molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy samples from 24 patients with idiopathic pulmonary fibrosis (IPF) and 17 control subjects. FKBP13 expression was found to be elevated in the fibrotic regions of IPF lung tissues, and within this cohort, was correlated with declining forced vital capacity and dyspnea severity. FKBP13 expression was also increased in lung biopsies of patients with hypersensitivity pneumonitis, rheumatoid arthritis, and sarcoidosis-associated interstitial lung disease. We next evaluated the role of this protein using FKBP13-/- mice in a bleomycin model of pulmonary fibrosis. Animals were assessed for lung function and histopathology at different stages of lung injury including the inflammatory (Day 7), fibrotic (Day 21) and resolution (Day 50) phase. FKBP13-/- mice showed increased infiltration of inflammatory cells and cytokines at Day 7, increased lung elastance and fibrosis at Day 21, and impaired resolution of fibrosis at Day 50. These changes were associated with an increased number of cells that stained positive for TUNEL and cleaved caspase 3 in the FKBP13-/- lungs, indicating a heightened cellular sensitivity to bleomycin. Our findings suggest that FKBP13 is a potential biomarker for severity or progression of interstitial lung diseases, and that it has a biologically relevant role in protecting mice against bleomycin-induced injury, inflammation and fibrosis.

Download Full-text

Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease

International Immunopharmacology ◽

10.1016/j.intimp.2021.107596 ◽

2021 ◽

Vol 97 ◽

pp. 107596

Author(s):

Qing Han ◽

Zhaohui Zheng ◽

Qiang Liang ◽

Xianghui Fu ◽

Fengfan Yang ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

B Cell ◽

Protective Role ◽

Cell Secretion

Download Full-text

Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope

PLoS ONE ◽

10.1371/journal.pone.0033133 ◽

2012 ◽

Vol 7 (5) ◽

pp. e33133 ◽

Cited By ~ 42

Author(s):

Hiroshi Furukawa ◽

Shomi Oka ◽

Kota Shimada ◽

Shoji Sugii ◽

Jun Ohashi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Human Leukocyte Antigen ◽

Lung Disease ◽

Shared Epitope ◽

Human Leukocyte ◽

Protective Role ◽

Leukocyte Antigen

Download Full-text

Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01226-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yueyan Lou ◽

Yu Zheng ◽

Bijun Fan ◽

Liyan Zhang ◽

Feng Zhu ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Serum Levels ◽

Clinical Severity

Download Full-text

Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

10.21203/rs.3.rs-15869/v1 ◽

2020 ◽

Author(s):

Yueyan Lou ◽

yu zheng ◽

Xiaoming Tan ◽

Bijun Fan ◽

Liyan Zhang ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Serum Levels ◽

Clinical Severity ◽

Enzyme Linked Immunosorbent Assay ◽

Inflammatory Disorder ◽

Healthy Controls ◽

Serum Samples ◽

High Resolution Computed Tomography ◽

Highly Correlated

Abstract Background: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods: Serum samples of 40 DM-ILD patients and 30 healthy controls were collected. Expressions of S100A8/A9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and interleukins were analyzed by cytometric beads array (CBA). Results: Serum IL-4, IL-6 and S100A8/A9 were observably higher in DM-ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = -0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = -0.2066, p = 0.0061, FVC%: r = -0.2156, p = 0.0050). Conclusions: Serum level of S100A8/A9 may be a valuable marker for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD. Keywords : Dermatomyositis, Interstitial lung disease, S100A8/A9, Interleukin

Download Full-text

Serum S100A12 levels are correlated with clinical severity in patients with dermatomyositis-associated interstitial lung disease

Journal of International Medical Research ◽

10.1177/0300060519887841 ◽

2019 ◽

Vol 48 (4) ◽

pp. 030006051988784

Author(s):

Yueyan Lou ◽

Yu Zheng ◽

Bijun Fan ◽

Liyan Zhang ◽

Feng Zhu ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Vital Capacity ◽

Pearson Correlation ◽

Clinical Severity ◽

Diffusing Capacity ◽

C Reactive Protein ◽

High Resolution Computed Tomography ◽

Reactive Protein ◽

Erythrocyte Sedimentation

Objective S100A12 is an emerging inflammatory disease biomarker. Interstitial lung disease (ILD) is a common, severe complication of dermatomyositis (DM). This study was performed to investigate the association between S100A12 and disease activity and prognosis in patients with DM-associated ILD (i.e., DM-ILD). Methods Serum S100A12 levels were measured using enzyme-linked immunosorbent assays in patients with stable DM-ILD, patients with acute exacerbation of DM-ILD (AE DM-ILD), and healthy controls (HCs). The relationships of serum S100A12 levels with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, high-resolution computed tomography (HRCT) scores, and pulmonary functions were evaluated by multiple unpaired t-tests and Pearson correlation. Results Serum S100A12 levels were higher in patients with stable DM-ILD and those with AE DM-ILD than in HCs. Serum S100A12 levels in patients with stable DM-ILD and those with AE DM-ILD were positively correlated with CRP, ESR, and ferritin. S100A12 levels were positively correlated with HRCT scores in patients with stable DM-ILD and those with AE DM-ILD, while they were negatively correlated with predicted percentages of forced vital capacity and predicted percentages of carbon monoxide diffusing capacity in those patients. Conclusion Our findings demonstrate the usefulness of serum S100A12 levels for assessing clinical severity and prognosis of DM-ILD.

Download Full-text