1,25-Dihydroxyvitamin D Modulates Antibacterial and Inflammatory Response in Human Cigarette Smoke-Exposed Macrophages

• Published in: PloS one Vol. 11; no. 8; p. e0160482
• Main Authors: Heulens, Nele, Korf, Hannelie, Mathyssen, Carolien, Everaerts, Stephanie, De Smidt, Elien, Dooms, Christophe, Yserbyt, Jonas, Gysemans, Conny, Gayan-Ramirez, Ghislaine, Mathieu, Chantal, Janssens, Wim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.08.2016; Public Library of Science (PLoS)
• Subjects: Alveoli; Antibacterial agents; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Cationic Peptides - metabolism; Bacteria; Biology and Life Sciences; Calcitriol; Care and treatment; Chemical properties; Chemokine CCL2 - metabolism; Chemokines; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Cigarettes; Cytokines; Defects; Diagnosis; Disease; E coli; Endocrinology; Enzymes; Escherichia coli; Exposure; Gene expression; Health aspects; Human behavior; Humans; Inflammation; Inflammatory response; Interferon; Interleukin 6; Interleukin 8; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Laboratories; Lipopolysaccharides; Lungs; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Medicine; Medicine and Health Sciences; Metabolism; Methods; Monocyte chemoattractant protein 1; Neutrophils; Phagocytosis; Phagocytosis - drug effects; Physical sciences; Respiratory Burst - drug effects; Respiratory diseases; Respiratory tract; Respiratory tract diseases; Risk factors; Rodents; Smoke; Smoking; Statistical analysis; Tobacco Products - toxicity; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; Vitamin deficiency; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160482

Cigarette smoking is associated with increased inflammation and defective antibacterial responses in the airways. Interestingly, vitamin D has been shown to suppress inflammation and to improve antibacterial defense. However, it is currently unknown whether vitamin D may modulate inflammation and antibacterial defects in human cigarette smoke (CS)-exposed airways. To explore these unresolved issues, alveolar macrophages obtained from non-smoking and smoking subjects as well as human cigarette smoke extract (CSE)-treated THP-1 macrophages were stimulated with 1,25-dihydroxyvitamin D (1,25(OH)2D) to address inflammatory and antibacterial responses. Although basal levels of inflammatory cytokines and chemokines did not differ between non-smoking and smoking subjects, 1,25(OH)2D did reduce levels of IL-6, TNF-α and MCP-1 in alveolar macrophages in response to LPS/IFN-γ, although not statistically significant for TNF-α and IL-6 in smokers. CSE did not significantly alter vitamin D metabolism (expression levels of CYP24A1 or CYP27B1) in THP-1 macrophages. Furthermore, stimulation with 1,25(OH)2D reduced mRNA expression levels and/or protein levels of IL-8, TNF-α and MCP-1 in CSE-treated THP-1 macrophages. 1,25(OH)2D did not improve defects in phagocytosis of E. coli bacteria or the oxidative burst response in CSE-treated THP-1 macrophages or alveolar macrophages from smokers. However, 1,25(OH)2D significantly enhanced mRNA expression and/or protein levels of the antimicrobial peptide cathelicidin in alveolar macrophages and THP-1 macrophages, independently of CS exposure. In conclusion, our results provide the first evidence that vitamin D could be a new strategy for attenuating airway inflammation and improving antibacterial defense in CS-exposed airways.