• ISSN 1674-8301
  • CN 32-1810/R
Turn off MathJax
Article Contents
Hwang Sung-Hyun, Yang Yeseul, Jeong Yeji, Kim Yongbaek. Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.35.20210012
Citation: Hwang Sung-Hyun, Yang Yeseul, Jeong Yeji, Kim Yongbaek. Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.35.20210012

Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx

doi: 10.7555/JBR.35.20210012
More Information
  • Corresponding author: Yongbaek Kim, Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Tel/Fax: +82-2-880-1273/+82-2-873-1213, E-mail: yongbaek@snu.ac.kr
  • Received: 2021-01-22
  • Revised: 2021-04-09
  • Accepted: 2021-04-14
  • Published: 2021-06-16
  • Atopic dermatitis (AD) is a common skin disorder difficult to be treated with medication. This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models. We found that, in canine macrophage cell line DH82, lipopolysaccharide (LPS) upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31 (IL-31) signaling, and the upregulation could be suppressed by ovalicin, with an effect significantly stronger than dexamethasone. Ovalicin also reduced the expression of IL-31 downstream genes, including JAK2 (Janus kinase 2), TRPV1 (transient receptor potential vanilloid receptor-1), and HRH2 (histamine receptor H2). Ovalicin significantly alleviated the allergic symptoms in the AD mouse model. Histologically, the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment. In the skin tissue of AD mice, reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment. To our knowledge, this is the first study to elucidate the anti-atopic mechanism of ovalicin, which could be an alternative to steroidal drugs commonly used for AD treatment.


  • loading
  • [1]
    Hong J, Buddenkotte J, Berger TG, et al. Management of itch in atopic dermatitis[J]. SeminCutan Med Surg, 2011, 30(2): 71–86. doi: 10.1016/j.sder.2011.05.002
    Wong LS, Wu T, Lee CH. Inflammatory and noninflammatory itch: implications in pathophysiology-directed treatments[J]. Int J Mol Sci, 2017, 18(7): 1485. doi: 10.3390/ijms18071485
    Szepietowski JC, Reich A. Pruritus in psoriasis: an update[J]. Eur J Pain, 2016, 20(1): 41–46. doi: 10.1002/ejp.768
    Hensel P, Santoro D, Favrot C, et al. Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification[J]. BMC Vet Res, 2015, 11(1): 196. doi: 10.1186/s12917-015-0515-5
    Simpson EL. Atopic dermatitis: a review of topical treatment options[J]. Curr Med Res Opin, 2010, 26(3): 633–640. doi: 10.1185/03007990903512156
    Coondoo A, Phiske M, Verma S, et al. Side-effects of topical steroids: a long overdue revisit[J]. Indian Dermatol Online J, 2014, 5(4): 416–425. doi: 10.4103/2229-5178.142483
    Bills GF, Gloer JB, An Z. Coprophilous fungi: antibiotic discovery and functions in an underexplored arena of microbial defensive mutualism[J]. Curr Opin Microbiol, 2013, 16(5): 549–565. doi: 10.1016/j.mib.2013.08.001
    Yoon CS, Nam SH, Jeon JY, et al. Ovalicin ameliorates compound 48/80-induced atopic dermatitis-related symptoms[J]. Biol Pharm Bull, 2011, 34(12): 1881–1884. doi: 10.1248/bpb.34.1881
    Meng J, Moriyama M, Feld M, et al. New mechanism underlying IL-31-induced atopic dermatitis[J]. J Allergy Clin Immunol, 2018, 141(5): 1677–1689. doi: 10.1016/j.jaci.2017.12.1002
    Furue M, Yamamura K, Kido-Nakahara M, et al. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis[J]. Allergy, 2018, 73(1): 29–36. doi: 10.1111/all.13239
    Takamori A, Nambu A, Sato K, et al. IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity[J]. Sci Rep, 2018, 8: 6639. doi: 10.1038/s41598-018-25094-4
    Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1[J]. J Allergy Clin Immunol, 2014, 133(2): 448–460. doi: 10.1016/j.jaci.2013.10.048
    Shim WS, Tak MH, Lee MH, et al. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase[J]. J Neurosci, 2007, 27(9): 2331–2337. doi: 10.1523/JNEUROSCI.4643-06.2007
    Rao X, Huang X, Zhou Z, et al. An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis[J]. Biostat Bioinforma Biomath, 2013, 3(3): 71–85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280562/
    Kim H, Kim JR, Kang H, et al. 7, 8, 4′-Trihydroxyisoflavone attenuates DNCB-induced atopic dermatitis-like symptoms in NC/Nga mice[J]. PLoS One, 2014, 9(8): e104938. doi: 10.1371/journal.pone.0104938
    Ku JM, Hong SH, Kim SR, et al. The prevention of 2, 4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo[J]. BMC Complement Altern Med, 2018, 18: 215. doi: 10.1186/s12906-018-2280-z
    Ulmer AJ, Flad HD, Rietschel T, et al. Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS)[J]. Toxicology, 2000, 152(1-3): 37–45. doi: 10.1016/S0300-483X(00)00290-0
    Ankers JM, Awais R, Jones NA, et al. Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation[J]. Elife, 2016, 5: e10473. doi: 10.7554/eLife.10473
    Yamaoka K, Okayama Y, Kaminuma O, et al. Proteomic approach to FcεRI aggregation-initiated signal transduction cascade in human mast cells[J]. Int Arch Allergy, 2009, 149(S1): 73–76. doi: 10.1159/000211376
    Jou IM, Lin CF, Tsai KJ, et al. Macrophage-mediated inflammatory disorders[J]. Mediators Inflamm, 2013, 2013: 316482. doi: 10.1155/2013/316482
    Hashimoto T, Kursewicz CD, Fayne RA, et al. Mechanisms of itch in stasis dermatitis: significant role of IL-31 from macrophages[J]. J Invest Dermatol, 2020, 140(4): 850–859. doi: 10.1016/j.jid.2019.09.012
    Elmariah SB, Lerner EA. Topical therapies for pruritus[J]. Semin Cutan Med Surg, 2011, 30(2): 118–126. doi: 10.1016/j.sder.2011.04.008
    Leslie TA, Greaves MW, Yosipovitch G. Current topical and systemic therapies for itch[M]//Cowan A, Yosipovitch G. Pharmacology of Itch. Berlin Heidelberg: Springer, 2015: 337–356.
    Perron G, Dolbec P, Germain J, et al. Perineal pruritus after iv dexamethasone administration[J]. Can J Anaesth, 2003, 50(7): 749–750. doi: 10.1007/BF03018722
    Kalthoff FS, Chung J, Stuetz A. Pimecrolimus inhibits up‐regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells[J]. Clin Exp Immunol, 2002, 130(1): 85–92. doi: 10.1046/j.1365-2249.2002.01962.x
    Drake LA, Millikan LE. The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Doxepin Study Group[J]. Arch Dermatol, 1995, 131(12): 1403–1408. doi: 10.1001/archderm.1995.01690240065010
    Kwon CY, Lee B, Kim S, et al. Effectiveness and safety of herbal medicine for atopic dermatitis: an overview of systematic reviews[J]. Evid Based Complement Alternat Med, 2020, 2020: 4140692. doi: 10.1155/2020/4140692
    Meister S, Plouffe DM, Kuhen KL, et al. Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery[J]. Science, 2011, 334(6061): 1372–1377. doi: 10.1126/science.1211936
    Kittaka H, Tominaga M. The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin[J]. Allergol Int, 2017, 66(1): 22–30. doi: 10.1016/j.alit.2016.10.003
    Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface[J]. QJM: Int J Med, 2003, 96(1): 7–26. doi: 10.1093/qjmed/hcg002
    Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity[J]. Biochem Biophys Res Commun, 2009, 388(4): 621–625. doi: 10.1016/j.bbrc.2009.08.062
    Dillon SR, Sprecher C, Hammond A, et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice[J]. Nat Immunol, 2004, 5(7): 752–760. doi: 10.1038/ni1084
  • JBR-2021-0012-supplementary.pdf
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(1)

    Article Metrics

    Article views (137) PDF downloads(21) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint