TY - JOUR
T1 - 1,25-dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages
AU - Chen, Yunzi
AU - Liu, Weicheng
AU - Sun, Tao
AU - Huang, Yong
AU - Wang, Youli
AU - Deb, Dilip K.
AU - Yoon, Dosuk
AU - Kong, Juan
AU - Thadhani, Ravi
AU - Li, Yan Chun
PY - 2013/4/1
Y1 - 2013/4/1
N2 - The negative feedbackmechanism is essential tomaintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH]2D 3) modulates innate immune response, but the mechanism remains poorly understood. In this article, we report that vitamin D receptor signaling attenuates TLR-mediated inflammation by enhancing the negative feedback inhibition. Vitamin D receptor inactivation leads to hyperinflammatory response in mice and macrophage cultures when challenged with LPS, because of microRNA-155 (miR-155) overproduction that excessively suppresses suppressor of cytokine signaling 1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates suppressor of cytokine signaling 1 by downregulating miR-155. 1,25(OH) 2D3 downregulates bic transcription by inhibiting NF-κB activation, which is mediated by a κB cis-DNA element located within the first intron of the bic gene. Together, these data identify a novel regulatory mechanism for vitamin D to control innate immunity.
AB - The negative feedbackmechanism is essential tomaintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH]2D 3) modulates innate immune response, but the mechanism remains poorly understood. In this article, we report that vitamin D receptor signaling attenuates TLR-mediated inflammation by enhancing the negative feedback inhibition. Vitamin D receptor inactivation leads to hyperinflammatory response in mice and macrophage cultures when challenged with LPS, because of microRNA-155 (miR-155) overproduction that excessively suppresses suppressor of cytokine signaling 1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates suppressor of cytokine signaling 1 by downregulating miR-155. 1,25(OH) 2D3 downregulates bic transcription by inhibiting NF-κB activation, which is mediated by a κB cis-DNA element located within the first intron of the bic gene. Together, these data identify a novel regulatory mechanism for vitamin D to control innate immunity.
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U2 - 10.4049/jimmunol.1203273
DO - 10.4049/jimmunol.1203273
M3 - Article
C2 - 23436936
AN - SCOPUS:84875437416
SN - 0022-1767
VL - 190
SP - 3687
EP - 3695
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -