Differential control of interleukin-6 mRNA levels by cellular distribution of YB-1.
Cytokine production is essential for innate and adaptive immunity against microbial invaders and must be tightly controlled. Cytokine messenger RNA (mRNA) is in constant flux between the nucleus and the cytoplasm and in transcription, splicing, or decay; such processes must be tightly controlled. Here, we report a novel function of Y-box-binding protein 1 (YB-1) in modulating interleukin-6 (IL-6) mRNA levels in a cell type-specific manner. In lipopolysaccharide (LPS)-stimulated macrophages, YB-1 interacts with IL-6 mRNA and actively transports it to the extracellular space by YB-1-enriched vesicles, resulting in the proper maintenance of intracellular IL-6 mRNA levels. YB-1 secretion occurs in a cell type-specific manner. Whereas macrophages actively secret YB-1, dendritic cells maintain it predominantly in the cytoplasm even in response to LPS. Intracellular YB-1 has the distinct function of regulating IL-6 mRNA stability in dendritic cells. Moreover, because LPS differentially regulates the expression of histone deacetylase 6 (HDAC6) in macrophages and dendritic cells, this stimulus might control YB-1 acetylation differentially in both cell types. Taken together, these results suggest a unique feature of YB-1 in controlling intracellular IL-6 mRNA levels in a cell type-specific manner, thereby leading to functions that are dependent on the extracellular and intracellular distribution of YB-1.
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Sujin
S
Kang
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Taeyun A
TA
Lee
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Eun A
EA
Ra
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Eunhye
E
Lee
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Hyun jin
Hj
Choi
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Sungwook
S
Lee
Department of Systems biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Boyoun
B
Park
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008156:Luciferases; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
D017931:DNA Primers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D008156:Luciferases