Open Access

Anti‑inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine‑stimulated keratinocytes

  • Authors:
    • Han‑Sol Lee
    • Ji‑Won Park
    • Ok‑Kyoung Kwon
    • Yourim Lim
    • Jung Hee Kim
    • Soo‑Yong Kim
    • Nelson Zamora
    • Kattia Rosales
    • Sangho Choi
    • Sei‑Ryang Oh
    • Kyung‑Seop Ahn
  • View Affiliations

  • Published online on: June 3, 2019     https://doi.org/10.3892/etm.2019.7639
  • Pages: 833-840
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti‑inflammatory and anti‑allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ‑stimulated HaCaT keratinocyte cells were investigated. ELISA and RT‑PCR analysis revealed that the extract had anti‑inflammatory effects, and reduced the interleukin (IL)‑6 and IL‑8 levels of the HaCaT cells. In addition, COEE exhibited anti‑allergic effects, comprising a reduction in the thymus and activation‑regulated chemokine and macrophage‑derived chemokine levels. In addition, pathway analysis and comparison with Bay11‑7082 indicated that these effects are due to the inhibition of nuclear factor (NF)‑κB in TNF‑α/IFN‑γ‑induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti‑inflammatory and anti‑allergic properties in TNF‑α and IFN‑γ‑stimulated HaCaT cells, which are associated with the inhibition of pro‑inflammatory cytokines and chemokines via the NF‑κB pathway.

Introduction

Atopic dermatitis (AD) is caused by a disturbance of the immune system. Therefore, to treat AD, it is necessary to normalize the immune system in addition to treating the external skin manifestations (13). Characteristic symptoms of AD are pruritus, pus, erythema and chronic skin bacterial infection. Skin barrier defects are recognized as one of the most important features of AD (46). The abnormal differentiation of skin epithelial cells causes skin barrier defects. These defects enable the infiltration of allergens, which induce an inflammatory reaction and systemic immunological reaction. These skin barrier defects are usually caused by genetic and acquired factors (7,8).

Keratinocytes are keratin-producing epidermal cells, which account for ~90% of epidermal cells (9,10). The main function of the epidermis is to provide a barrier that protects the human body from environmental factors, including pathogens, heat, ultraviolet rays and moisture loss. Thymic stromal lymphopoietin (TSLP) present in keratinocytes stimulates dendritic cells to increase the production of thymus and activation-regulated chemokine [TARC; also known as chemokine (C-C motif) ligand 17, CCL17] and macrophage-derived chemokine (MDC; also known as CCL22) (11,12). TARC and MDC are typical type 2 helper T cell (Th2 cell)-secreted chemokines that induce Th2 cell recruitment at inflammatory sites (13). High concentrations of TARC, MDC and TSLP have been detected in patients with AD (14). These biomarkers are known to be very closely associated with atopic disease (15,16).

Cedrela odorata L. is a plant of the genus Cedrela and is distributed across tropical climate regions, such as the Amazon (17,18). Its wood is mainly used as raw material for household furniture or musical instruments (19). Traditionally, C. odorata L. has been utilized in folk remedies for diarrhea, fever, inflammation, vomiting, hemorrhage, and indigestion (20,21). However, since there is no literature regarding this plant in relation to inflammation or AD, it was investigated in the present study. The aim of the study was to examine the biochemical activity of C. odorata L. ethanol extract (COEE) using HaCaT cells induced with a mixture of tumor necrosis factor (TNF)-α and interferon (IFN)-γ.

Materials and methods

Preparation of COEE

The leaves and shoots of C. odorata L. were collected in Palo Verde National Park, Costa Rica, in 2014. A voucher specimen (KRIB 0056657) has been deposited at the International Biological Material Research Center (IBMRC) in the Korea Research Institute of Bioscience and Biotechnology (Daejeon, South Korea). The dried and refined leaves and shoots of C. odorata (100 g) were extracted with 700 ml 95% ethanol for 2 h, three times. The extract was percolated through filter paper (3 mm; Whatman PLC, Kent, UK), condensed using a rotary evaporator (Büchi AG, Flawil, Switzerland) and lyophilized using a freeze dryer (Martin Christ Gefriertrocknungsanlagen, Osterode am Harz, Germany).

Cell culture

The human keratinocyte HaCaT cell line was purchased from the American Tissue Culture Center (Manassas, VA, USA). Cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco; Thermo Fisher Scientific, Inc. Waltham, MA, USA) containing 10% fetal bovine serum (Gibco; Thermo Fisher Scientific, Inc.) and 1% penicillin-streptomycin, and maintained using an incubator at temperature 37°C with a 5% CO2 atmosphere while maintaining a confluency of 60–80%.

MTT assay

Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. HaCaT cells were seeded in 96-well plates (SPL Life Sciences, Pocheon, Korea) at a density of 1×104 cells/well. After 6 h of incubation, COEE (1.25, 2.5, 5, 10 and 20 µg/ml) was administered and the cells were incubated for 24 h at 37°C. Untreated cells were defined as the control group. Next, 5 µl MTT solution (5 mg/ml; Amresco, LLC, Solon, OH, USA) was added to the cell supernatant, and the mixture was incubated for 4 h at 37°C. After removing the medium, DMSO was added to dissolve the formazan. A microplate reader was used to measure the absorbance at 570 nm, and the untreated formazan value was set at 100%.

Cytokine assay

HaCaT cells were cultured in 96-well plates at a density of 5×104 cells/well. After an incubation for 6 h at 37°C, COEE (2.5, 5, 10 and 20 µg/ml) and Bay11-7082 (5 µM) were administered. TNF-α/IFN-γ (10 ng/ml of each; TNF-α cat. no. 300-01A; IFN-γ cat. no. 300-02; PeproTech, Inc., Rocky Hill, NJ, USA) was applied 1 h later. The next day, the supernatant was harvested. The inhibitory effect of COEE on the secretion of interleukin (IL)-6, IL-8, TARC and MDC into the supernatants was evaluated using the following ELISA kits: IL-6 (cat. no. 555220; BD Biosciences, Santa Clara, CA, USA), IL-8 (cat. no. DY208), TARC (cat. no. DY364) and MDC (cat. no. DY336; all R&D Systems, Inc., Minneapolis, MN, USA). Samples were analyzed according to the manufacturer's protocol.

RT-PCR analysis

Total RNA was extracted from the cells using TRIzol® reagent (Invitrogen, Thermo Fisher Scientific, Inc.). Following isolation of the RNA, cDNA synthesis was performed using a QuantiTect Reverse Transcription kit (cat. no. 205310; Qiagen GmbH, Hilden, Germany). RNA, gDNA Wipeout Buffer and RNase-free water were mixed and incubated at 42°C for 2 min. Then, Quantiscript Reverse Transcriptase, Quantiscript RT Buffer and RT River Mix were mix with the aforementioned reagents and incubated at 42°C for 15 min. Finally, the mixture was incubated at 95°C for 3 min to inactivate Quantiscript Reverse Transcriptase. The synthesized cDNA was amplified by PCR using a GoTaq® Green Master mix (Promega Corporation, Madison, WI, USA) with 11 pmol of each primer. The sequences of the RT-PCR primers used in the present study are listed in Table I. β-actin was used as the reference gene. The thermocycling conditions were as follows: Pre-denaturation at 94°C for 5 min, then 25 cycles of denaturation at 94°C for 20 sec, annealing at 56°C for 20 sec and extension at 72°C for 45 sec. The reaction products were separated by electrophoresis on a 1.5% agarose gel and stained with RedSafe™ kits (Intron Biotechnology, Inc., Seongnam, Korea). Images were captured using an Olympus C4000 zoom camera system (Olympus Corporation). The densitometry of the bands were measured using ImageJ 1.50i software (National Institutes of Health, Bethesda, MD, USA).

Table I.

Sequences of the reverse transcription PCR primers used in the current study.

Table I.

Sequences of the reverse transcription PCR primers used in the current study.

GeneDirectionPrimer sequences (human; 5′-3′)Fragment size (bp)
TARCForwardCAC GCA GCT CGA GGG ACC AAT GTG222
ReverseTCA AGA CCT CTC AAG GCT TTG CAG G
MDCForwardAGG ACA GAG CAT GGC TCG CCT ACA GA362
ReverseTAA TGG CAG GGA GGT AGG GCT CCT GA
IL-6ForwardGAC AGC CAC TCA CCT CTT CA124
ReverseAGT GCC TCT TTGCTG CTT TC
IL-8ForwardATG ACT TCC AAG CTG GCC GTG GCT299
ReverseTTA TGA ATT CTC AGC CCT CTT CAA AAA
β-actinForwardCAT GTA CGT TGC TAT CCA GGC250
ReverseCTC CTT AAT GTC ACG CAC GAT

[i] IL, interleukin; TARC, thymus and activation-regulated chemokine; MDC, macrophage-derived chemokine.

Immunoblotting

Immunoblotting of the cells was performed as previously described (22). The HaCaT cells were pre-treated with the indicated concentrations of COEE (2.5, 5. 10 and 20 µg/ml) for 1 h and stimulated with TNF-α/IFN-γ (10 ng/ml each) for 20 min at 37°C. Immunoblots were created using anti-nuclear factor (NF)-κB p65 (cat. no. sc-8242; Santa Cruz Biotechnology, Inc., Dallas, TX, USA), anti-phospho-NF-κB inhibitor α (anti-p-IκBα; cat. no. 2859), anti-IκB-α (cat. no. 9242), anti-NF-κB p-p65 (cat. no. 3033) and anti-β-actin (cat. no. 4967; all 1:1,000; all from Cell Signaling Technology, Inc., Danvers, MA, USA). The secondary antibodies were horseradish peroxidase-conjugated goat anti-rabbit IgG (cat. no. sc-2030; 1:5,000 in 5% skimmed milk; Santa Cruz Biotechnology, Inc.). The densitometry of the bands were measured using ImageJ 1.50i software.

Luciferase assay

HaCaT cells were transfected with 0.1 µg pGL4.32 (luc2P/NF-κB-RE/Hygro) plasmids (Promega Corporation), using Lipofectamine 2000 transfection reagent (Invitrogen; Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol. At 24 h after transfection, the cells were pretreated with COEE (2.5, 5, 10 and 20 µg/ml) and Bay11-7082 (5 µM) for 1 h at 37°C, stimulated with TNF-α/IFN-γ for 20 h at 37°C, harvested and then assessed for luc2P luciferase activity using the ONE-Glo™ luciferase reporter assay system (Promega Corporation) according to the manufacturer's instructions. Normalization was performed by comparison with Renilla luciferase activity.

Statistical analysis

Data are presented as the mean ± SEM. Statistical differences among groups were determined by one-way ANOVA with repeated measures followed by Newman-Keuls testing using SPSS version 14.0 software (IBM Corp., Armonk, NY, USA). P<0.05 was considered to indicate a statistically significant difference.

Results

Cytotoxic effects of COEE in HaCaT cells

Whether COEE affects the viability of HaCaT cells was analyzed using the MTT assay. As shown in Fig. 1, COEE did not exhibit cytotoxicity and did not affect cell viability even when used at a high concentration of 20 µg/ml for 24 h. This confirmed experimentally that COEE does not exhibit toxicity in HaCaT cells at concentrations ≤20 µg/ml.

COEE inhibits TNF-α/IFN-γ-induced IL-6 and IL-8 expression in HaCaT cells

Next, ELISA and RT-PCR assays were used to study the inhibitory effect of COEE on the production of IL-6 and IL-8 in HaCaT cells stimulated with TNF-α/IFN-γ. The RT-PCR results confirmed that the levels of IL-6 and IL-8 were significantly increased in the group treated with TNF-α/IFN-γ compared with those in the untreated group. Similarly, when TNF-α/IFN-γ was added after the introduction of COEE to HaCaT cells, the mRNA expression levels of IL-6 and IL-8 decreased in an apparently concentration-dependent manner compared with those in the group treated with TNF-α/IFN-γ without COEE (Fig. 2A). Furthermore, the ELISA results demonstrated that COEE inhibited the expression of the IL-6 and IL-8 proteins in HaCaT cells stimulated with TNF-α/IFN-γ compared with those in the cells treated with TNF-α/IFN-γ without COEE (Fig. 2B and C).

COEE inhibits TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression in HaCaT cells

Chemokines are significant mediators of the inflammatory reaction and immune response. Exposure of keratinocytes to TNF-α/IFN-γ induces the increased expression of chemokines, leading to the infiltration of leukocytes into inflammatory lesions in the skin (23,24). In the present study, ELISA and RT-PCR were used to investigate the suppressive effect of COEE on TARC and MDC production in TNF-α/IFN-γ-stimulated HaCaT cells. The RT-PCR results confirmed that TARC and MDC mRNA levels were significantly increased in the cells treated with TNF-α/IFN-γ compared with those in the untreated group. Similarly, when TNF-α/IFN-γ was added after the application of COEE to the HaCaT cells, the mRNA expression levels of TARC and MDC decreased compared with those in the group treated with TNF-α/IFN-γ without COEE, and the reduction appeared to be concentration-dependent (Fig. 3A). Furthermore, the ELISA results indicated that COEE inhibited the expression of the TARC and MDC proteins in HaCaT cells induced with TNF-α/IFN-γ (Fig. 3B and C).

COEE inhibits the phosphorylation of NF-κB p65 in HaCaT cells

The nuclear factor NF-κB signaling pathway is considered a prototypical pro-inflammatory pathway, mainly due to the role of NF-κB in the expression of pro-inflammatory genes, for example, adhesion molecules, chemokines and cytokines (25). Therefore, NF-κB p65 phosphorylation in TNF-α/IFN-γ-treated HaCaT cells was analyzed in the present study. The western blotting results indicated that the phosphorylation of IκBα and NF-κB p65 was significantly increased by TNF-α/IFN-γ-treatment, whereas pretreatment with COEE attenuated the TNF-α/IFN-γ-induced increase in p-IκBα and p-p65 levels (Fig. 4).

COEE and Bay11-7082 inhibit the phosphorylation of NF-κB in HaCaT cells

Bay11-7082 inhibits IκBα phosphorylation in cells and has been used to indicate the involvement of the canonical IκB kinases and NF-κB in mechanistic analysis (26). A comparative experiment was conducted in the present study, in which the efficacy of COEE (20 µg/ml) was compared with that of Bay11-7082 (5 µM) in the inhibition of NF-κB p65. Phosphorylation of IκBα and NF-κB p65 was significantly increased by TNF-α/IFN-γ-treatment, while pretreatment with COEE and Bay11-7082 decreased the levels of p-p65 and p-IκBα in TNF-α/IFN-γ-treated HaCaT cells, as indicated by the results of immunoblotting and the luciferase assay (Fig. 5).

COEE and Bay11-7082 inhibit the expression of chemokines and cytokines in HaCaT cells

Using ELISA and RT-PCR, the suppressive effects of COEE and Bay11-7082 on TARC, MDC, IL-6 and IL-8 production in HaCaT cells stimulated with TNF-α/IFN-γ were investigated. The results confirmed that the levels of TARC, MDC, IL-6 and IL-8 were significantly increased in the group treated with TNF-α/IFN-γ compared with those in the untreated group. However, when TNF-α/IFN-γ was added after the introduction of COEE and Bay11-7082 to the HaCaT cells, the mRNA and protein expression levels of TARC, MDC, IL-6 and IL-8 decreased in an apparently concentration-dependent manner compared with those in the group treated with TNF-α/IFN-γ without COEE (Fig. 6).

Discussion

AD, also known as eczema, is a common chronic inflammatory skin disease and is characterized by the infiltration of inflammatory cells into the skin (27). Although AD is generally treated with immunosuppressive drugs and anti-inflammatory drugs, these treatments are often ineffective (28). This may cause patients to use alternative treatment strategies, including traditional plant-based remedies.

In the present study, in vitro experiments were conducted to determine the effects of COEE on pro-inflammatory chemokine secretion in keratinocytes. Keratinocytes serve a crucial role in inflammatory skin disorders via the production of pro-inflammatory cytokines and chemokines (29). These cells participate in the pathogenesis of AD by secreting various chemokines, among which TARC and MDC selectively attract Th2 cells that are predominant in atopic inflammation (30). IL-8 amplifies the inflammatory response in AD by recruiting neutrophils into the skin lesions (31). Numerous researchers have reported that TNF-α/IFN-γ treatment increases chemokine production in keratinocytes (32,33). The TNF-α/IFN-γ combination activates several intracellular pathways, including NF-κB pathways (34,35). NF-κB pathways have been shown to be involved in the regulation of chemokine and cytokine production in keratinocyte cells; they serve a significant role in the immune response and regulate inflammatory signaling (36,37). Therefore, experiments to investigate the effect of COEE on the TNF-α/IFN-γ-stimulated expression of MDC and TARC in HaCaT cells were conducted in the present study.

The NF-κB family includes critical transcription factors that are activated by various stimuli, including TNF-α, IFN-γ, IL-1 and lipopolysaccharide. Upon stimulation, NF-κB complexes in the cytoplasm translocate into the nucleus, where they participate in the expression of numerous pro-inflammatory genes (22). NF-κB signaling pathways have been shown to be involved in the regulation of TARC and MDC production in HaCaT cells (38). Furthermore, the promoters of TARC and MDC both contain NF-κB-binding sites (39), indicating that these transcription factors may be involved in the modulation of TARC and MDC (38). In the present study, the results indicated that COEE suppressed signaling pathways leading to the activation of TARC and MDC by NF-κB.

Treatment with COEE or the IκBα inhibitor Bay11-7082 reduced the TNF-α/IFN-γ-activated expression of pro-inflammatory cytokines (IL-6 and IL-8) and chemokines (TARC and MDC) to baseline values. These results indicate that COEE reduces the production of the pro-inflammatory cytokines IL-6 and IL-8, and the expression of the Th2 chemokines TARC and MDC in HaCaT cells via inhibition of NF-κB pathways in HaCaT cells. These effects are hypothesized to be closely associated with the suppression of NF-κB activation. Therefore, it is suggested that COEE has the potential to be used as a therapeutic drug for the treatment of AD.

In conclusion, the results of the present study indicate that COEE inhibits the TNF-α/IFN-γ-stimulated expression of TARC and MDC in HaCaT cells via the inhibition of NF-κB pathways. The ability of COEE to suppress the formation of these Th2 chemokines suggests that it may be able to inhibit the infiltration of Th2 cells into skin lesions and thereby reduce skin inflammation. Further investigation of the mechanism by which COEE inhibits the release of these Th2 chemokines may provide insights helpful in the design of targeted treatments for AD. However, additional studies using in vivo skin inflammation models are required to support the potential of COEE in the clinical treatment of AD.

Acknowledgements

Not applicable.

Funding

The present study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIT; grant no. NRF-2016K1A1A8A01939075) and the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program of the Republic of Korea (grant no. KGM5521911). The authors thank the National Biodiversity Institute and Tempisque Conservation Area for preparing the plant materials.

Availability of data and materials

The analyzed datasets generated during the study are available from the corresponding author upon reasonable request.

Authors' contributions

HSL and JWP analyzed the data and wrote the manuscript. OKK, YL, JHK, SYK, NZ and KR prepared the Cedrela odorata L., and analyzed and edited the manuscript. SC, SRO, and KSA designed the study and edited the manuscript. All authors critically revised the article and have approved the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Elbadawy HM, Borthwick F, Wright C, Martin PE and Graham A: Cytosolic StAR-related lipid transfer domain 4 (STARD4) protein influences keratinocyte lipid phenotype and differentiation status. Br J Dermatol. 164:628–632. 2011.PubMed/NCBI

2 

Hong SW, Choi EB, Min TK, Kim JH, Kim MH, Jeon SG, Lee BJ, Gho YS, Jee YK, Pyun BY and Kim YK: An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus. PLoS One. 9:e1004992014. View Article : Google Scholar : PubMed/NCBI

3 

Elmariah SB and Lerner EA: The missing link between itch and inflammation in atopic dermatitis. Cell. 155:267–269. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Fuhlbrigge RC, Kieffer JD, Armerding D and Kupper TS: Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature. 389:978–981. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Boguniewicz M and Leung DY: Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev. 242:233–246. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Oyoshi MK, He R, Kumar L, Yoon J and Geha RS: Cellular and molecular mechanisms in atopic dermatitis. Adv Immunol. 102:135–226. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Ou LS and Huang JL: Cellular aspects of atopic dermatitis. Clin Rev Allergy Immunol. 33:191–198. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Li C, Lasse S, Lee P, Nakasaki M, Chen SW, Yamasaki K, Gallo RL and Jamora C: Development of atopic dermatitis-like skin disease from the chronic loss of epidermal caspase-8. Proc Natl Acad Sci USA. 107:22249–22254. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Metral E, Bechetoille N, Demarne F, Damour O and Rachidi W: Keratinocyte stem cells are more resistant to UVA radiation than their direct progeny. PLoS One. 13:e02038632018. View Article : Google Scholar : PubMed/NCBI

10 

Orazizadeh M, Hashemitabar M, Bahramzadeh S, Dehbashi FN and Saremy S: Comparison of the enzymatic and explant methods for the culture of keratinocytes isolated from human foreskin. Biomed Rep. 3:304–308. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Qi XF, Kim DH, Yoon YS, Li JH, Jin D, Teng YC, Kim SK and Lee KJ: Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon-gamma in HaCaT cells, a human keratinocyte cell line. Br J Pharmacol. 157:1441–1450. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Wilson SR, Thé L, Batia LM, Beattie K, Katibah GE, McClain SP, Pellegrino M, Estandian DM and Bautista DM: The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell. 155:285–295. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Hirata H, Arima M, Cheng G, Honda K, Fukushima F, Yoshida N, Eda F and Fukuda T: Production of TARC and MDC by naive T cells in asthmatic patients. J Clin Immunol. 23:34–45. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Ying S, O'Connor B, Ratoff J, Meng Q, Mallett K, Cousins D, Robinson D, Zhang G, Zhao J, Lee TH and Corrigan C: Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol. 174:8183–8190. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Liu YJ: Thymic stromal lymphopoietin: Master switch for allergic inflammation. J Exp Med. 203:269–273. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Leyva-Castillo JM, Hener P, Jiang H and Li M: TSLP produced by keratinocytes promotes allergen sensitization through skin and thereby triggers atopic march in mice. J Invest Dermatol. 133:154–163. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Veitch NC, Wright GA and Stevenson PC: Four new tetranortriterpenoids from Cedrela odorata associated with leaf rejection by exopthalmus jekelianus. J Nat Prod. 62:1260–1263. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Navarro C, Ward S and Hernandez M: The tree Cedrela odorata (Meliaceae): A morphologically subdivided species in Costa Rica. Rev Biol Trop. 50:21–29. 2002.PubMed/NCBI

19 

Thu PQ, Quang DN and Dell B: Threat to cedar, Cedrela odorata, plantations in Vietnam by the weevil, Aclees sp. J Insect Sci. 10:1922010. View Article : Google Scholar : PubMed/NCBI

20 

Millan-Orozco L, Corredoira E and San José Mdel C: In vitro rhizogenesis: Histoanatomy of Cedrela odorata (Meliaceae) microcuttings. Rev Biol Trop. 59:447–453. 2011.PubMed/NCBI

21 

Wu WB, Zhang H, Dong SH, Sheng L, Wu Y, Li J and Yue JM: New triterpenoids with protein tyrosine phosphatase 1B inhibition from Cedrela odorata. J Asian Nat Prod Res. 16:709–716. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Park JW, Kwon OK, Yuniato P, Marwoto B, Lee J, Oh SR, Kim JH and Ahn KS: Amelioration of an LPS-induced inflammatory response using a methanolic extract of Lagerstroemia ovalifolia to suppress the activation of NF-κB in RAW264.7 macrophages. Int J Mol Med. 38:482–490. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Choi JH, Jin SW, Park BH, Kim HG, Khanal T, Han HJ, Hwang YP, Choi JM, Chung YC, Hwang SK, et al: Cultivated ginseng inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice and TNF-α/IFN-γ-induced TARC activation in HaCaT cells. Food Chem Toxicol. 56:195–203. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Jung MR, Lee TH, Bang MH, Kim H, Son Y, Chung DK and Kim J: Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 3-O-β-D-glucopyanosylspinasterol via blocking NF-κB and STAT1 signaling pathways in TNF-α and IFN-γ-induced HaCaT keratinocytes. Biochem Biophys Res Commun. 427:236–241. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 1:a0016512009. View Article : Google Scholar : PubMed/NCBI

26 

Strickson S, Campbell DG, Emmerich CH, Knebel A, Plater L, Ritorto MS, Shpiro N and Cohen P: The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system. Biochem J. 451:427–437. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Voorhees T, Chang J, Yao Y, Kaplan MH, Chang CH and Travers JB: Dendritic cells produce inflammatory cytokines in response to bacterial products from Staphylococcus aureus-infected atopic dermatitis lesions. Cell Immunol. 267:17–22. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Megna M, Napolitano M, Patruno C, Villani A, Balato A, Monfrecola G, Ayala F and Balato N: Systemic treatment of adult atopic dermatitis: A review. Dermatol Ther (Heidelb). 7:1–23. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Lee JW, Park HA, Kwon OK, Park JW, Lee G, Lee HJ, Lee SJ, Oh SR and Ahn KS: NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation. Mol Immunol. 90:150–157. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Kakinuma T, Nakamura K, Wakugawa M, Mitsui H, Tada Y, Saeki H, Torii H, Asahina A, Onai N, Matsushima K and Tamaki K: Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol. 107:535–541. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Park JW, Shin IS, Ha UH, Oh SR, Kim JH and Ahn KS: Pathophysiological changes induced by Pseudomonas aeruginosa infection are involved in MMP-12 and MMP-13 upregulation in human carcinoma epithelial cells and a pneumonia mouse model. Infect Immun. 83:4791–4799. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Lim SJ, Kim M, Randy A, Nam EJ and Nho CW: Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells. J Pharm Pharmacol. 68:1465–1479. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Park JW, Lee HS, Lim Y, Kwon OK, Kim JH, Paryanto I, Yunianto P, Choi S, Oh SR and Ahn KS: Rhododendron album Blume extract inhibits TNF-α/IFN-γ-induced chemokine production via blockade of NF-κB and JAK/STAT activation in human epidermal keratinocytes. Int J Mol Med. 41:3642–3652. 2018.PubMed/NCBI

34 

Park JW, Kwon OK, Kim JH, Oh SR, Kim JH, Paik JH, Marwoto B, Widjhati R, Juniarti F, Irawan D and Ahn KS: Rhododendron album Blume inhibits iNOS and COX-2 expression in LPS-stimulated RAW264.7 cells through the downregulation of NF-κB signaling. Int J Mol Med. 35:987–994. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Park JW, Lee IC, Shin NR, Jeon CM, Kwon OK, Ko JW, Kim JC, Oh SR, Shin IS and Ahn KS: Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling. Nanotoxicology. 10:445–452. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Choi JK and Kim SH: Inhibitory effect of galangin on atopic dermatitis-like skin lesions. Food Chem Toxicol. 68:135–141. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Yang JH, Yoo JM, Cho WK and Ma JY: Anti-inflammatory effects of Sanguisorbae Radix water extract on the suppression of mast cell degranulation and STAT-1/Jak-2 activation in BMMCs and HaCaT keratinocytes. BMC Complement Altern Med. 16:3472016. View Article : Google Scholar : PubMed/NCBI

38 

Kwon DJ, Bae YS, Ju SM, Goh AR, Youn GS, Choi SY and Park J: Casuarinin suppresses TARC/CCL17 and MDC/CCL22 production via blockade of NF-κB and STAT1 activation in HaCaT cells. Biochem Biophys Res Commun. 417:1254–1259. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Nakayama T, Hieshima K, Nagakubo D, Sato E, Nakayama M, Kawa K and Yoshie O: Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein-Barr virus. J Virol. 78:1665–1674. 2004. View Article : Google Scholar : PubMed/NCBI

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July-2019
Volume 18 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Lee HS, Park JW, Kwon OK, Lim Y, Kim JH, Kim SY, Zamora N, Rosales K, Choi S, Oh SR, Oh SR, et al: Anti‑inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine‑stimulated keratinocytes. Exp Ther Med 18: 833-840, 2019
APA
Lee, H., Park, J., Kwon, O., Lim, Y., Kim, J.H., Kim, S. ... Ahn, K. (2019). Anti‑inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine‑stimulated keratinocytes. Experimental and Therapeutic Medicine, 18, 833-840. https://doi.org/10.3892/etm.2019.7639
MLA
Lee, H., Park, J., Kwon, O., Lim, Y., Kim, J. H., Kim, S., Zamora, N., Rosales, K., Choi, S., Oh, S., Ahn, K."Anti‑inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine‑stimulated keratinocytes". Experimental and Therapeutic Medicine 18.1 (2019): 833-840.
Chicago
Lee, H., Park, J., Kwon, O., Lim, Y., Kim, J. H., Kim, S., Zamora, N., Rosales, K., Choi, S., Oh, S., Ahn, K."Anti‑inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine‑stimulated keratinocytes". Experimental and Therapeutic Medicine 18, no. 1 (2019): 833-840. https://doi.org/10.3892/etm.2019.7639