Inhibition of Poly(I:C)-Induced Inflammation by Salvianolic Acid A in Skin Keratinocytes = Inhibition of Poly(I:C)-Induced Inflammation by Salvianolic Acid A in Skin Keratinocytes

다국어 초록 (Multilingual Abstract)

Background: Skin keratinocytes participate actively in inducing immune responses when external pathogens are introduced, thereby contributing to elimination of pathogens. However, in condition where the excessive inflammation is occurred, chronic skin disease such as psoriasis can be provoked. Objective: We tried to screen the putative therapeutics for inflammatory skin disease, and found that salvianolic acid A (SAA) has an inhibitory effect on keratinocyte inflammatory reaction. The aim of this study is to demonstrate the effects of SAA in poly(I:C)-induced inflammatory reaction in skin keratinocytes. Methods: We pre-treated keratinocytes with SAA then stimulated with poly(I:C). Inflammatory reaction of keratinocytes was verified using real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot. Results: When skin keratinocytes were pre-treated with SAA, it significantly inhibited poly (I:C)-induced expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and CCL20. SAA inhibited poly(I:C)-induced activation of nuclear factor-κB signaling. And SAA also inhibited inflammasome activation, evidenced by decrease of IL-1β secretion. Finally, SAA markedly inhibited poly(I:C)-induced NLRP3 expression. Conclusion: These results demonstrate that SAA has an inhibitory effect on poly(I:C)-induced inflammatory reaction of keratinocytes, suggesting that SAA can be developed for the treatment of inflammatory skin diseases such as psoriasis. (Ann Dermatol 31(3) 279∼285, 2019)

참고문헌 (Reference)

1 Fischetti L, "The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling" 99 : 287-296, 2017

2 Sohn KC, "The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes" 37 : 1099-1104, 2016

3 Muruve DA, "The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response" 452 : 103-107, 2008

4 Kim J, "The immunopathogenesis of psoriasis" 33 : 13-23, 2015

5 Rudraiah S, "TNIP1 reduction sensitizes keratinocytes to post-receptor signalling following exposure to TLR agonists" 45 : 81-92, 2018

6 Grimstad Ø, "TLR3 mediates release of IL-1β and cell death in keratinocytes in a caspase-4dependent manner" 72 : 45-53, 2013

7 Pei R, "Salvianolic acid A, a novel PI3K/Akt inhibitor, induces cell apoptosis and suppresses tumor growth in acute myeloid leukemia" 59 : 1959-1967, 2018

8 Lian-Niang L, "Salvianolic acid A, a new depside from roots of salvia miltiorrhiza" 50 : 227-228, 1984

9 Zheng X, "Salvianolic acid A reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating transgelin 2" 16 : 1407-1414, 2015

10 Yuan X, "Salvianolic acid A protects against myocardial ischemia/reperfusion injury by reducing platelet activation and inflammation" 14 : 961-966, 2017

11 Li L, "Salvianolic acid A attenuates cell apoptosis, oxidative stress, Akt and NF-κB activation in angiotensin-II induced murine peritoneal macrophages" 17 : 283-290, 2016

12 Fan HY, "Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats" 5 : 12273-, 2015

13 Chien MY, "Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice" 99 : 508-519, 2016

14 Li ZJ, "Roles of TLR7 in activation of NF-κB signaling of keratinocytes by imiquimod" 8 : e77159-, 2013

15 Hawkes JE, "Psoriasis pathogenesis and the development of novel targeted immune therapies" 140 : 645-653, 2017

16 Greb JE, "Psoriasis" 2 : 16082-, 2016

17 Rana AA, "Poly(I : C)induces controlled release of IL-36γ from keratinocytes in the absence of cell death" 63 : 228-235, 2015

18 Zhu S, "Peptide GC31inhibits chemokines and ICAM-1 expression in corneal fibroblasts exposed to LPS or poly(I : C)by blocking the NF-κB and MAPK pathways" 164 : 109-117, 2017

19 Grimstad O, "Oligodeoxynucleotides inhibit Toll-like receptor 3 mediated cytotoxicity and CXCL8 release in keratinocytes" 21 : 7-12, 2012

20 Ding C, "New insights into salvianolic acid A action : regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats" 6 : 28734-, 2016

21 Choi HI, "Melanosome uptake is associated with the proliferation and differentiation of keratinocytes" 306 : 59-66, 2014

22 Sweeney CM, "Innate immunity in the pathogenesis of psoriasis" 303 : 691-705, 2011

23 Elliott EI, "Initiation and perpetuation of NLRP3inflammasome activation and assembly" 265 : 35-52, 2015

24 Zheng Jun Li, "Induction of Interleukin-22 (IL-22) production in CD4+ T Cells by IL-17A Secreted from CpG-Stimulated Keratinocytes" 대한피부과학회 28 (28): 579-585, 2016

25 Lebre MC, "Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9" 127 : 331-341, 2007

26 Carlström M, "Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility" 21 : 932-937, 2012

27 Vu AT, "Extracellular double-stranded RNA induces TSLP via an endosomal acidification-and NF-κB-dependent pathway in human keratinocytes" 131 : 2205-2212, 2011

28 Trinchieri G, "Cooperation of Toll-like receptor signals in innate immune defence" 7 : 179-190, 2007

29 Sun Y, "CCN1promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis" 7 : 43310-, 2017

30 Nemes Z, "Bricks and mortar of the epidermal barrier" 31 : 5-19, 1999