title: 1,25-Dihydroxyvitamin D Modulates Antibacterial and Inflammatory Response in Human Cigarette Smoke-Exposed Macrophages.
abstract: 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.
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Nele
authors: N
authors: Heulens
authors: Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Hannelie
authors: H
authors: Korf
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Carolien
authors: C
authors: Mathyssen
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Stephanie
authors: S
authors: Everaerts
authors: Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Elien
authors: E
authors: De Smidt
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Christophe
authors: C
authors: Dooms
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Jonas
authors: J
authors: Yserbyt
authors: Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Conny
authors: C
authors: Gysemans
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Ghislaine
authors: G
authors: Gayan-Ramirez
authors: Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Chantal
authors: C
authors: Mathieu
authors: Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Wim
authors: W
authors: Janssens
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D062789:Tobacco Products / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D054804:Cathelicidins