Abstract
Human surfactant protein D (SP-D) is a potent innate immune molecule, which is emerging as a key molecule in the recognition and clearance of altered and non-self targets. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis via p53-mediated apoptosis pathway in an eosinophilic leukemic cell line, AML14.3D10. Here, we report the ability of rfhSP-D to induce apoptosis via TNF-α/Fas-mediated pathway regardless of the p53 status in human pancreatic adenocarcinoma using Panc-1 (p53mt), MiaPaCa-2 (p53mt), and Capan-2 (p53wt) cell lines. Treatment of these cell lines with rfhSP-D for 24 h caused growth arrest in G1 cell cycle phase and triggered transcriptional upregulation of pro-apoptotic factors such as TNF-α and NF-κB. Translocation of NF-κB from the cytoplasm into the nucleus of pancreatic cancer cell lines was observed via immunofluorescence microscopy following treatment with rfhSP-D as compared to the untreated cells. The rfhSP-D treatment caused upregulation of pro-apoptotic marker Fas, as analyzed via qPCR and western blot, which then triggered caspase cascade, as evident from cleavage of caspase 8 and 3 analyzed via western blot at 48 h. The cell number following the rfhSP-D treatment was reduced in the order of Panc-1 (~67%) > MiaPaCa-2 (~60%) > Capan-2 (~35%). This study appears to suggest that rfhSP-D can potentially be used to therapeutically target pancreatic cancer cells irrespective of their p53 phenotype.
Highlights
Human surfactant protein D (SP-D), a member of soluble C-type lectin family called Collectins, plays a vital role in linking the innate and adaptive immunity to protect against infection, allergy, and inflammation [1]
No CY5 or FITC fluorescence was detected in the untreated controls, probed with primary and secondary antibodies, for each cell line, suggesting the recombinant fragment of human SP-D (rfhSP-D) and Full length native SP-D (FL-SP-D) binding observed in the treated cell lines was protein-specific
Growth arrest at 24 h following rfhSP-D treatment prompted the determination of cell fate at a later time point; all cell lines were analyzed for likely apoptosis at 48 h
Summary
Human surfactant protein D (SP-D), a member of soluble C-type lectin family called Collectins, plays a vital role in linking the innate and adaptive immunity to protect against infection, allergy, and inflammation [1]. SP-D gene knockout mice showed chronic inflammation and fibrosis due to accumulation of surfactant phospholipids in the lungs, monocytes infiltration, and activation of pro-inflammatory alveolar macrophages [5, 6]. The absence of SP-D in children makes them more susceptible to frequent pneumonia as compared to Immune Surveillance by SP-D in Pancreatic Cancer. SFTPD (SP-D gene) polymorphisms increase the susceptibility to chronic and infectious lung diseases [8], pneumococcal lung disease [9], emphysema [10], tuberculosis [11, 12], Crohn’s disease, and ulcerative colitis [12]
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