共 43 条
Activation of Toll-like Receptor 2 (TLR2) induces Interleukin-6 trans-signaling
被引:47
作者:
Flynn, Charlotte M.
[1
]
Garbers, Yvonne
[2
]
Lokau, Juliane
[1
,6
]
Wesch, Daniela
[3
]
Schulte, Dominik M.
[4
]
Laudes, Matthias
[4
]
Lieb, Wolfgang
[5
]
Aparicio-Siegmund, Samadhi
[1
]
Garbers, Christoph
[1
,6
]
机构:
[1] Univ Kiel, Inst Biochem, Kiel, Germany
[2] Univ Kiel, Inst Psychol, Kiel, Germany
[3] Univ Hosp Schleswig Holstein, Inst Immunol, Campus Kiel, Kiel, Germany
[4] Univ Kiel, Dept Internal Med 1, Kiel, Germany
[5] Univ Kiel, Inst Epidemiol, Kiel, Germany
[6] Otto von Guericke Univ, Med Fac, Dept Pathol, Magdeburg, Germany
关键词:
NF-KAPPA-B;
SOLUBLE IL-6R;
CUTTING EDGE;
BLOCKADE;
BIOLOGY;
GENE;
EXPRESSION;
CYTOKINE;
ADAM10;
SERUM;
D O I:
10.1038/s41598-019-43617-5
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Signaling of the pleiotropic cytokine Interleukin-6 (IL-6) via its soluble IL-6R (sIL-6R) has been termed trans-signaling and is thought to be responsible for the pro-inflammatory properties of IL-6. The sIL-6R can be generated by alternative mRNA splicing or proteolytic cleavage of the membrane-bound IL-6R. However, which stimuli induce sIL-6R release and which endogenous signaling pathways are required for this process is poorly understood. Here, we show that activation of Toll-like receptor 2 (TLR2) on primary human peripheral blood mononuclear cells (PBMCs) and on the monocytic cell line THP-1 induces expression and secretion of IL-6 and the generation of sIL-6R. We show by flow cytometry that monocytes are a PBMC subset that expresses TLR2 in conjunction with the IL-6R and are the major cellular source for both IL-6 and sIL-6R. Mechanistically, we find that the metalloproteases ADAM10 and ADAM17 are responsible for cleavage of the IL-6R and therefore sIL-6R generation. Finally, we identify the Extracellular-signal Regulated Kinase (ERK) cascade as a critical pathway that differentially regulates both IL-6 and sIL-6R generation in monocytes.
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页数:11
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