Increased Expression of CC16 in Patients with Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology. The pathogenic mechanisms are unclear, but evidence indicates that aberrantly activated alveolar epithelial cells secrete a variety of mediators which induce the migration, proliferation and activation of fibroblasts and finally the excessive accumulation of extracellular matrix with the consequent destruction of the lung parenchyma. CC16 (approved symbol SCGB1A1), a putative anti-inflammatory protein produced by “club” cells in the distal airways, has not been evaluated in IPF lungs. In this study, we determined the serum and bronchoalveolar lavage (BAL) levels as well as the lung cell localization of this protein. Also, we explored the usefulness of serum levels of CC16 for the differential diagnosis of IPF (n = 85), compared with non-IPF interstitial lung diseases [chronic hypersensitivity pneumonitis (cHP; n = 85) and connective tissue diseases (CTD-ILD; n = 85)]. CC16 was significantly increased in serum and BAL fluids of IPF patients and was found not only in club cells but also in alveolar epithelial cells. When compared with non-IPF patients and controls, serum levels were significantly increased (p<0.0001). Sensitivity and specificity for CC16 (cut-off 41ng/mL) were 24% and 90%, positive predictive value 56% and negative predictive value 69%. These findings demonstrate that CC16 is upregulated in IPF patients suggesting that may participate in its pathogenesis. Although higher than the serum levels of non-IPF patients it shows modest sensitivity to be useful as a potential biomarker for the differential diagnosis.

Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype

“…BAL pellets from patients diagnosed with IPF or hypersensitivity pneumonitis [ 30 ], diagnosed according to published consensus statements were received as 1 ml frozen pellets. The local ethics committee of the Instituto Nacional de Enfremedades Respiratorias (INER, Mexico City, Mexico) approved the human BAL study.…”

CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling

“…Further, other studies have observed an expansion of KRT5 + cells into the alveolar parenchyma of bleomycin-injured or influenza-infected mouse lungs (12,13), with one study suggesting that these cells may be distinct from airway basal and club cells (12). Consistently, several studies have reported an expansion of KRT5 + and SCGB1A1 + epithelial cells in fibrotic IPF lungs (14)(15)(16); however, the role of these epithelial cells in the relentless and progressive lung remodeling observed in this disease remains elusive.…”

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in a human iPSC‐derived air‐liquid interface model

“…As our model system contains rare individual KRT5 + basal‐like cells, their role in the IPF‐RC mediated effects cannot be excluded. However, as IPF‐RC treatment of small airway basal cells induced a strong upregulation of MUC5AC , but not MUC5B , contrary to the abundant emergence of aberrant MUC5B + cells in the bronchiolized distal airspaces in IPF patients, as well as suppressed the expression of transcripts upregulated in the IPF lung such as SCGB1A1 and FOXJ1, the airway‐like phenotype observed in iPSC‐derived IPF‐RC cultures is unlikely the sole result of basal‐like cell expansion and differentiation 5,6,76,77 . Moreover, IPF‐RC stimulation did not induce proliferation of primary small airway basal cells compared to controls.…”