Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model

  • Jung Ok Lee (Department of Dermatology, College of Medicine, Chung-Ang University) ;
  • Youna Jang (Department of Dermatology, College of Medicine, Chung-Ang University) ;
  • A Yeon Park (Department of Dermatology, College of Medicine, Chung-Ang University) ;
  • Jung Min Lee (Department of Dermatology, College of Medicine, Chung-Ang University) ;
  • Kyeongsoo Jeong (Research and Development Center, Green Cross Wellbeing Corporation) ;
  • So-Hyun Jeon (Research and Development Center, Green Cross Wellbeing Corporation) ;
  • Hui Jin (Research and Development Center, Green Cross Wellbeing Corporation) ;
  • Minju Im (Research and Development Center, Green Cross Wellbeing Corporation) ;
  • Jae-Won Kim (Research and Development Center, Green Cross Wellbeing Corporation) ;
  • Beom Joon Kim (Department of Dermatology, College of Medicine, Chung-Ang University)
  • Received : 2024.06.28
  • Accepted : 2024.08.28
  • Published : 2024.10.28
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Abstract

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Keywords

Acknowledgement

We are grateful to Dr. Dong-Hwan Kim for assisting with ideas and the experimental design.

References

  1. Peng W, Novak N. 2015. Pathogenesis of atopic dermatitis. Clin. Exp. Allergy 45: 566-574.
  2. Thomsen SF. 2014. Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy 2014: 354250.
  3. Otsuka A, Nomura T, Rerknimitr P, Seidel JA, Honda T, Kabashima K. 2017. The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis. Immunol. Rev. 278: 246-262.
  4. Bin L, Leung DY. 2016. Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin. Immunol. 12: 52.
  5. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. 2004. New insights into atopic dermatitis. J. Clin. Invest. 113: 651-657.
  6. Novak N, Bieber T. 2003. Allergic and nonallergic forms of atopic diseases. J. Allergy Clin. Immunol. 112: 252-262.
  7. Agrawal R, Woodfolk JA. 2014. Skin barrier defects in atopic dermatitis. Curr. Allergy Asthma Rep. 14: 433.
  8. Proksch E, Folster-Holst R, Brautigam M, Sepehrmanesh M, Pfeiffer S, Jensen JM. 2009. Role of the epidermal barrier in atopic dermatitis. J. Dtsch Dermatol. Ges. 7: 899-910.
  9. Nicol NH. 2005. Anatomy and physiology of the skin. Dermatol. Nurs. 17: 62.
  10. Mori T, Ishida K, Mukumoto S, Yamada Y, Imokawa G, Kabashima K, et al. 2010. Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis. Br. J. Dermatol. 162: 83-90.
  11. Mestrallet G, Rouas-Freiss N, LeMaoult J, Fortunel NO, Martin MT. 2021. Skin immunity and tolerance: focus on epidermal keratinocytes expressing HLA-G. Front. Immunol. 12: 772516.
  12. Nygaard U, Hvid M, Johansen C, Buchner M, Folster-Holst R, Deleuran M, et al. 2016. TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis. J. Eur. Acad. Dermatol. Venereol. 30: 1930-1938.
  13. Elias PM, Schmuth M. 2009. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr. Allergy Asthma Rep. 9: 265-272.
  14. Chieosilapatham P, Kiatsurayanon C, Umehara Y, Trujillo-Paez JV, Peng G, Yue H, et al. 2021. Keratinocytes: innate immune cells in atopic dermatitis. Clin. Exp. Immunol. 204: 296-309.
  15. Seegraber M, Srour J, Walter A, Knop M, Wollenberg A. 2018. Dupilumab for treatment of atopic dermatitis. Expert. Rev. Clin. Pharmacol. 11: 467-474.
  16. Wollenberg A, Blauvelt A, Guttman-Yassky E, Worm M, Lynde C, Lacour JP, et al. 2021. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol. 184: 437-449.
  17. Bieber T, Simpson EL, Silverberg JI, Thaci D, Paul C, Pink AE, et al. 2021. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl. J. Med. 384: 1101-1112.
  18. Queille C, Pommarede R, Saurat JH. 1984. Efficacy versus systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood. Pediatr. Dermatol. 1: 246-253.
  19. Czarnowicki T, Krueger JG, Guttman-Yassky E. 2017. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J. Allergy Clin. Immunol. 139: 1723-1734.
  20. Noreen S, Maqbool I, Madni A. 2021. Dexamethasone: therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur. J. Pharmacol. 894: 173854.
  21. Poggioli R, Ueta CB, Drigo RA, Castillo M, Fonseca TL, Bianco AC. 2013. Dexamethasone reduces energy expenditure and increases susceptibility to diet-induced obesity in mice. Obesity (Silver Spring) 21: E415-420.
  22. Shen S, Liao Q, Liu J, Pan R, Lee SM, Lin L. 2019. Myricanol rescues dexamethasone-induced muscle dysfunction via a sirtuin 1-dependent mechanism. J. Cachexia Sarcopenia Muscle 10: 429-444.
  23. Chang PY, Chin LC, Kimura K, Nakahata Y. 2022. Human placental extract activates a wide array of gene expressions related to skin functions. Sci. Rep. 12: 11031.
  24. Kwon TR, Oh CT, Choi EJ, Park HM, Han HJ, Ji HJ, et al. 2015. Human placental extract exerts hair growth-promoting effects through the GSK-3beta signaling pathway in human dermal papilla cells. Int. J. Mol. Med. 36: 1088-1096.
  25. Lee TH, Park DS, Jang JY, Lee I, Kim JM, Choi GS, et al. 2019. Human placenta hydrolysate promotes liver regeneration via activation of the cytokine/growth factor-mediated pathway and anti-oxidative effect. Biol. Pharm. Bull. 42: 607-616.
  26. Shin EH, Kim M, Hada B, Oh CT, Jang MJ, Kim JY, et al. 2019. Effects of human placenta extract (Laennec) on ligament healing in a rodent model. Biol. Pharm. Bull. 42: 1988-1995.
  27. Bak DH, Na J, Choi MJ, Lee BC, Oh CT, Kim JY, et al. 2018. Anti-apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro. Int. J. Mol. Med. 42: 2569-2583.
  28. Kim EH, Kim YI, Jang SG, Im M, Jeong K, Choi YK, et al. 2021. Antiviral effects of human placenta hydrolysate (Laennec((R))) against SARS-CoV-2 in vitro and in the ferret model. J. Microbiol. 59: 1056-1062.
  29. Lee KH, Kim TH, Lee WC, Kim SH, Lee SY, Lee SM. 2011. Anti-inflammatory and analgesic effects of human placenta extract. Nat. Prod. Res. 25: 1090-1100.
  30. Lee S-H, Kang J-H, Kang D-J. 2016. Anti-allergic effect of Lactobacillus rhamnosus IDCC 3201 isolated from breast milk-fed Korean infant. Kor. J. Microbiol. 52: 18-24.
  31. Lee JW, Wu Q, Jang YP, Choung SY. 2018. Pinus densiflora bark extract ameliorates 2, 4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice by regulating Th1/Th2 balance and skin barrier function. Phytother. Res. 32: 1135-1143.
  32. Liu J, Han X, Zhang T, Tian K, Li Z, Luo F. 2023. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy. J. Hematol. Oncol. 16: 116.
  33. Rizwan S, ReddySekhar P, MalikAsrar B. 2014. Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling.
  34. Elisyutina O, Fedenko E, Shabanova I, Karimova I, Elisyutina O, Fedenko E, et al. 2010. The experience of atopic dermatitis treatment Wit «Laennek»(«Japan bioproducts industry Co., LTD», JAPAN) in Russia. Russian J. Allergy 7: 97-104.
  35. Bak Dh, Na J, Im SI, Oh CT, Kim JY, Park SK, et al. 2019. Antioxidant effect of human placenta hydrolysate against oxidative stress on muscle atrophy. J. Cell. Physiol. 234: 1643-1658.
  36. Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y. 2009. Mast cells in atopic dermatitis. Curr. Opin. Immunol. 21: 666-678.
  37. Mack MR, Kim BS. 2018. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol. 39: 980-991.
  38. Esnault S, Kelly EA. 2016. Essential mechanisms of differential activation of eosinophils by IL-3 compared to GM-CSF and IL-5. Crit. Rev. Immunol. 36: 429-444.
  39. Song TW, Sohn MH, Kim ES, Kim KW, Kim KE. 2006. Increased serum thymus and activation-regulated chemokine and cutaneous T cell-attracting chemokine levels in children with atopic dermatitis. Clin. Exp. Allergy 36: 346-351.
  40. Luster AD. 2002. The role of chemokines in linking innate and adaptive immunity. Curr. Opin. Immunol. 14: 129-135.
  41. Marques-Mejias A, Bartha I, Ciaccio CE, Chinthrajah RS, Chan S, Hershey GKK, et al. 2024. Skin as the target for allergy prevention and treatment. Annals of Allergy, Asthma & Immunology.
  42. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, et al. 2017. Antimicrobials from human skin commensal bacteria protect against and are deficient in atopic dermatitis. Sci. Transl. Med. 9.
  43. Smith AR, Knaysi G, Wilson JM, Wisniewski JA. 2017. The skin as a route of allergen exposure: part I. immune components and mechanisms. Curr. Allergy Asthm. R. 17.
  44. Nicotera P, Melino G. 2007. Caspase-14 and epidermis maturation. Nat. Cell Biol. 9: 621-622.
  45. Denecker G, Hoste E, Gilbert B, Hochepied T, Ovaere P, Lippens S, et al. 2007. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat. Cell Biol. 9: 666-U101.
  46. Kim BE, Leung DYM. 2018. Significance of skin barrier dysfunction in atopic dermatitis. Allergy Asthma Immun. 10: 207-215.
  47. Cultrone A, de Wouters T, Lakhdari O, Kelly D, Mulder I, Logan E, et al. 2013. The NF-κB binding site located in the proximal region of the TSLP promoter is critical for TSLP modulation in human intestinal epithelial cells. Eur. J. Immunol. 43: 1053-1062.