Anti‑inflammation activity of brazilin in TNF‑α induced human psoriasis dermatitis skin model

다국어 초록 (Multilingual Abstract)

Psoriasis is a chronic inflammatory skin disease that causes erythema, scale, and invasion due to excessive proliferation of keratinocyte and vascular deformation of the upper part of the dermis. Recently, it has been reported that brazilin, an active compound of Caesalpinia sappan L., possesses anti-inflammatory activity in mouse macrophage.
However, little is known about its effect or anti-inflammatory activity on psoriasis dermatitis. Thus, the objective of this study was to determine anti-inflammatory activity of brazilin in TNF-α-induced human keratinocyte (HaCaT) widely used as a model of psoriatic dermatitis. First, CCK-8 assay was performed to determine cytotoxicity of brazilin in HaCaT cells and cytotoxicity was not observed up to 7 μg/mL concentrations. Brazilin decreased mRNA expression levels of inflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8 and TNF-α in a concentration dependent manner.
Brazilin also significantly reduced phosphorylation of I-κB, Akt, and MAPKs such as ERK, JNK, p38 and STAT3 in immortalized human keratinocytes (HaCaT) induced by TNF-α. In addition, inflammation causes the weakness of the skin barrier structure and increase cell permeability, stimulating serious problems in skin moisturizing. Thus, we observed changes of skin permeability in TNF-α induced inflammatory condition through transepithelial electrical resistance (TEER) assay. While TNF-α induced inflammation caused reduction of TEER value (ohm (Ω) × cm2), it was recovered by treatment with brazilin in a concentration-dependent manner. These results strongly imply that brazilin can reinforce the skin barrier due to its anti-inflammatory activity. Therefore, brazilin could be a promising candidate for treating psoriasis dermatitis.

참고문헌 (Reference)

1 Sun W, "‘Psoriasis 1′reduces psoriasis-like skin inflammation by inhibiting the VDR-mediated nuclear NF-κB and STAT signaling pathways" 18 : 2733-2743, 2018

2 Johansen C, "The mitogen-activated protein kinases p38 and ERK1/2are increased in lesional psoriatic skin" 152 : 37-42, 2005

3 Naldi L, "The clinical spectrum of psoriasis" 25 : 510-518, 2007

4 Gianello V, "The PDE4 inhibitor CHF6001 modulates pro-inflammatory cytokines, chemokines and Th1-and Th17-polarizing cytokines in human dendritic cells" 163 : 371-380, 2019

5 Bradley JR, "TNF-mediated inflammatory disease" 214 : 149-160, 2008

6 Chen G, "TNF-R1 signaling : a beautiful pathway" 296 : 1634-1635, 2002

7 Bae IK, "Suppression of lipopolysaccharide-induced expression of inducible nitric oxide synthase by brazilin in RAW 2647 macrophage cells" 513 : 237-242, 2005

8 Son ED, "Staphylococcus aureus inhibits terminal differentiation of normal human keratinocytes by stimulating interleukin-6 secretion" 74 : 64-71, 2014

9 Arthur JSC, "Signaling downstream of p38 in psoriasis" 126 : 1689-1691, 2006

10 Baud V, "Signal transduction by tumor necrosis factor and its relatives" 11 : 372-377, 2001

11 최다희, "RAW264.7 대식세포에서 MAPK 및 NF-κB 신호전달 억제를 통한 rebaudioside A의 항염 효과" 한국응용생명화학회 61 (61): 205-211, 2018

12 Nakajima K, "Mouse models of psoriasis and their relevance" 45 : 252-263, 2018

13 Bocheńska K, "Models in the research process of psoriasis" 18 : 2514-, 2017

14 조경아, "Interleukin-17 and Interleukin-22 Induced Proinflammatory Cytokine Production in Keratinocytes via Inhibitor of Nuclear FactorκB Kinase-α Expression" 대한피부과학회 24 (24): 398-405, 2012

15 Bachelez H, "Immunopathogenesis of psoriasis : recent insights on the role of adaptive and innate immunity" 25 : 69-73, 2005

16 Yu S, "Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis" 2 : 4-14, 2019

17 Hunter CA, "IL-6 as a keystone cytokine in health and disease" 16 : 448-457, 2015

18 Shi X, "IL-17A upregulates keratin 17 expression in keratinocytes through STAT1-and STAT3-dependent mechanisms" 131 (131): 2401-2408, 2011

19 Xiong H, "Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice and inhibits TNF-a-induced ICAM-1 expression via NF-κB/MAPK in HaCaT cells" 35 : 1335-1346, 2015

20 Wang A, "Genistein suppresses psoriasis-related inflammation through a STAT3–NF-κB-dependent mechanism in keratinocytes" 69 : 270-278, 2019

21 Arnott CH, "Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development" 23 : 1902-1910, 2004

22 Yokouchi M, "Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum" 77 : 28-36, 2015

23 Hwang GS, "Effects of brazilin on the phospholipase A 2 activity and changes of intracellular free calcium concentration in rat platelets" 21 : 774-778, 1998

24 Roux PP, "ERK and p38 MAPK-activated protein kinases : a family of protein kinases with diverse biological functions" 68 : 320-344, 2004

25 조욱민, "Deoxynivalenol Impair Skin Barrier Function through the Down Regulation of Filaggrin and Claudin 1/8 in HaCaT Keratinocyte" 한국생물공학회 22 (22): 693-699, 2017

26 Baliwag J, "Cytokines in psoriasis" 73 : 342-350, 2015

27 Kryczek I, "Cutting edge : IFN-γ enables APC to promote memory Th17 and abate Th1cell development" 181 : 5842-5846, 2008

28 Guttman-Yassky E, "Contrasting pathogenesis of atopic dermatitis and psoriasis—part I : clinical and pathologic concepts" 127 : 1110-1118, 2011

29 Sun Y, "CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis" 7 : 43310-, 2017

30 Moon CK, "Brazilin protects cultured rat hepatocytes from BrCCI3-induced toxicity" 15 : 81-91, 1992

31 Hwang HS, "Brazilin and Caesalpinia sappan L. extract protect epidermal keratinocytes from oxidative stress by inducing the expression of GPX7" 16 : 203-209, 2018

32 Xu H, "Anti-malarial agent artesunate inhibits TNF-α-induced production of proinflammatory cytokines via inhibition of NF-κB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes" 46 : 920-926, 2007

33 Rogerio AP, "Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma" 56 : 402-408, 2007

34 Blauvelt A, "Allergic and immunologic diseases of the skin" 111 : S560-S570, 2003

35 Patel TN, "A review of high-dose statin therapy : targeting cholesterol and inflammation in atherosclerosis" 28 : 664-672, 2007