Title |
IL-37 Suppresses MyD88-mediated Inflammatory Responses in Human Aortic Valve Interstitial Cells
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Published in |
Molecular Medicine, March 2017
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DOI | 10.2119/molmed.2017.00022 |
Pubmed ID | |
Authors |
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A. Fullerton, Charles A. Dinarello, Xianzhong Meng |
Abstract |
Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists. Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide, respectively, in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor inducing interferon-β (TRIF) differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced the production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced the induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain. Activation of TLR2, TLR3 or TLR4 up-regulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This anti-inflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Doctoral Student | 5 | 19% |
Researcher | 4 | 15% |
Student > Bachelor | 3 | 12% |
Student > Master | 3 | 12% |
Student > Postgraduate | 2 | 8% |
Other | 3 | 12% |
Unknown | 6 | 23% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 3 | 12% |
Agricultural and Biological Sciences | 3 | 12% |
Immunology and Microbiology | 3 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 2 | 8% |
Unknown | 9 | 35% |