Effects of 1α,25 Dihydroxyvitamin D₃ on Pro-inflammatory Cytokines of Palmitic Acid Treated Thp-1 Cells

Abstract: The level of saturated fatty acids, such as palmitic acid (PA), correlates with chronic inflammation in obese and metabolic syndrome patients. However, low level of vitamin D₃ is observed in those conditions. The aim of this study is to investigate effects of 1α,25(OH)₂D₃ on PA-treated THP-1 cells. Using quantitative real-time polymerase chain reaction, we measure mRNA expression of pro-inflammatory cytokines: TNF-α, Interleukin (IL)-1β, IL-6, and chemokine IL-8 under PA and 1α,25(OH)₂D₃ influence. PA, at all concentrations (25–100 μM), enhanced LPS stimulatory effect on those mRNA expression compared to LPS-treated and -untreated cells. Combination with 1α,25(OH)₂D₃ increased cytokine expression at high (10⁻⁶ M) and high-normal (10⁻⁸ M) concentrations compared to PA + LPS and LPS alone, both for 2 and 24 h. However, low-normal (10⁻¹⁰ M) and low (10⁻¹² M) levels of 1α,25(OH)₂D₃ could not enhance PA effect, but mRNA expression of pro-inflammatory cytokine was higher than LPS-treated cells. Upstream pathway of 1α,25(OH)₂D₃, which is cholecalciferol, also gave the similar result. Further, inhibition of calcium pathway does not play a role in this mechanism. Thus, these findings support pro-inflammatory effect of PA and vitamin D₃ on innate immune response, especially on fat-induced inflammation. Practical Application: The effect of vitamin D₃ on chronic inflammation in obesity is uncertain. This study shows an in vitro possibility that vitamin D₃ could exaggerate inflammation when combined with high SFAs. The idea of using vitamin D₃ supplement to modulate inflammation in fat-related inflammation needs further refined experiments before its clinical application.