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Vitamin D 3 Metabolites Enhance the NLRP3‐Dependent Secretion of IL‐1β From Human THP‐1 Monocytic Cells
Author(s) -
Tulk Sarah E.,
Liao KuoChieh,
Muruve Daniel A.,
Li Yan,
Beck Paul L.,
MacDonald Justin A.
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24985
Subject(s) - calcitriol receptor , inflammasome , thp1 cell line , cyp24a1 , vitamin d and neurology , immune system , vitamin d binding protein , vitamin , secretion , chemistry , cytokine , medicine , western blot , endocrinology , biology , receptor , cell culture , biochemistry , immunology , genetics , gene
Vitamin D 3 has emerged as an important regulator of the immune system. With metabolic enzymes for vitamin D 3 activation and vitamin D receptors (VDR) now identified in a variety of immune cells, the active vitamin D 3 metabolite 1,25(OH) 2 D 3 , is thought to possess immunomodulatory properties. We examined whether 1,25(OH) 2 D 3 might also enhance the NLRP3‐dependent release of mature IL‐1β from macrophages. PMA‐differentiated THP‐1 cells were stimulated with vitamin D 3 metabolites and assessed for CYP27, CYP24, NLRP3, ASC, pro‐caspase‐1 expression by western blot and real‐time qPCR as well as inflammasome activation with pro‐inflammatory cytokine IL‐1β release measured by ELISA. Exposure to 1,25(OH) 2 D 3 had no effect on the basal expression levels of VDR; however, CYP27A1 transcript was suppressed and CYP24A1 transcript was substantively elevated. Both 1,25(OH) 2 D 3 ‐ and 25(OH)D 3 induced IL‐1β release from THP‐1 cells, and these effects were blocked with application of the caspase‐1 inhibitor YVAD and the NLRP3 inhibitors glyburide and Bay 11–7082. Interestingly, 1,25 (OH) 2 D 3 exposure reduced NLRP3 protein expression but had no effect on ASC or pro‐caspase‐1 protein levels. The increase in mature IL‐1β elicited by 1,25(OH) 2 D 3 was modest compared to that found for ATP or C. difficile toxins. However, co‐treatment of THP‐1 cells with ATP and 1,25(OH) 2 D 3 resulted in more IL‐1β secretion than ATP or 1,25(OH) 2 D 3 alone. J. Cell. Biochem. 116: 711–720, 2015. © 2015 Wiley Periodicals, Inc.