DOI QR코드

DOI QR Code

Der p 1에 의한 정상인과 알레르기 환자의 림프구에서 사이토카인 분비를 통한 자발적인 호중구 세포고사 억제

Der p 1 Inhibits Spontaneous Neutrophil Apoptosis by Cytokine Secretion of Normal and Allergic Lymphocytes

  • 김인식 (대전 을지대학교 임상병리학과) ;
  • 이나래 (대전 을지대학교 임상병리학과) ;
  • 이지숙 (원광보건대학교 임상병리학과)
  • Kim, In Sik (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Lee, Na Rae (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Lee, Ji-Sook (Department of Clinical Laboratory Science, Wonkwang Health Science University)
  • 투고 : 2014.10.07
  • 심사 : 2014.10.26
  • 발행 : 2015.12.30

초록

Dermatophagoides pteronissinus (DP)는 알레르기 질환과 연관이 있는 집먼지 진드기 중 하나이다. 집먼지 진드기에 의해 생성되는 Cystein 단백질분해효소(Derp-1)가 강력한 알레르겐으로 작용한다. 알레르기 병인기전은 림프구의 사이토카인 분비와 호중구의 자발적인 세포고사와 연관이 있다. 본 연구에서는 Derp-1이 림프구에서 사이토카인 분비를 유도하는지 여부와 이에 의해 호중구 세포고사 조절에 영향을 주는지를 실험 해보았다. 정상인과 알레르기 환자의 림프구에서, Derp-1에 의해 IL-6, IL-8, MCP-1그리고 GM- CSF의 분비가 증가됨을 보였다. Derp-1이 단독으로 호중구에 영향을 주는 것은 아니지만, Derp-1으로 호중구를 자극한 뒤 모은 상층액이 호중구의 세포고사를 억제시킴을 확인하였다. 정상인의 호중구와 림프구를 co-culture하여 Derp-1을 처리한 결과 호중구의 세포고사가 억제되었고, 이보다 알레르기 환자에서 시행되어진 것이 그 효과가 더 크게 나타났다. 즉, Derp-1은 사이토카인의 분비를 증가시키고, 이로 인해 정상인과 알레르기 환자의 호중구의 세포고사를 억제시킨다. 이를 통해 알레르기 질환의 병인기전을 밝히는데 유용한 자료가 될 수 있을 것으로 사료된다.

Dermatophagoides pteronissinus (DP) is one of the house dust mites (HDM) associated with allergic diseases. The cysteine protease Der p 1 from DP is a powerful allergen. The pathogenic mechanism of allergy is involved in cytokine secretion of lymphocytes and spontaneous apoptosis of neutrophils. In this study, we investigated whether Der p 1 induces cytokine secretion of lymphocytes and if the release of cytokines is associated with regulation of neutrophil apoptosis. In normal and allergic subjects, Der p 1 increased IL-6, IL-8, MCP-1, and GM-CSF release in a time-dependent course. Supernatants collected from normal and allergic neutrophils after Der p 1 stimulation suppressed the apoptosis of normal and allergic neutrophils, although Der p 1 alone has no effect on neutrophils. Der p 1 suppressed neutrophil apoptosis in coculture of normal neutrophils with normal lymphocytes. Der p 1 more strongly suppressed apoptosis of allergic neutrophils cocultured with allergic lymphocytes than normal neutrophils cocultured with normal lymphocytes. In summary, Der p 1 increases the secretion of cytokines, which has anti-apoptotic effects on neutrophils of normal and allergic subjects. These results will contribute to elucidate the pathogenic mechanism of allergic diseases.

키워드

참고문헌

  1. Allen JE, Sutherland TE, Ruckerl D. IL-17 and neutrophils: unexpected players in the type 2 immune response. Curr Opin Immunol. 2015, 34:99-106. https://doi.org/10.1016/j.coi.2015.03.001
  2. Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006, 8 Suppl 2:S3.
  3. Ghaemmaghami AM, Robins RA, Gough L, Sewell HF, Shakib F. Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-g. Eur J Immunol. 2001, 31:1211-1216. https://doi.org/10.1002/1521-4141(200104)31:4<1211::AID-IMMU1211>3.0.CO;2-R
  4. Ghaemmaghami AM, Gough L, Sewell HF, Shakib F. The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level. Clin Exp Allergy. 2002, 32:1468-1475. https://doi.org/10.1046/j.1365-2745.2002.01504.x
  5. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy. 2008, 38:872-897 https://doi.org/10.1111/j.1365-2222.2008.02971.x
  6. Kang BK, Kim MA, Park SH, Lee EJ, Kim JS, Kim EJ, et al. The house dust mite allergen, Dermatophagoides pteronyssinus regulates the constitutive apoptosis and cytokine secretion of human eosinophils. Biomed Sci Lett. 2014, 20:39-42.
  7. Kim DH, Choi E, Lee JS, Lee NR, Baek SY, Gu A, et al. House dust mite allergen regulates constitutive apoptosis of normal and asthmatic neutrophils via toll-like receptor 4. PLoS One. 2015, 10:e0125983. https://doi.org/10.1371/journal.pone.0125983
  8. Kim EH, Lee JS, Lee NR, Baek SY, Kim EJ, Lee SJ, et al. Regulation of constitutive neutrophil apoptosis due to house dust mite allergen in normal and allergic rhinitis subjects. PLoS One. 2014, 9:e105814. https://doi.org/10.1371/journal.pone.0105814
  9. Kim IS, Kim EH, Kim DH, Kim JS, Lee JS. Effect of house dust mite and CCL2 on S100A8 and S100A9 expression in human monocytes. Biomed Sci Lett. 2013, 19: 344-347.
  10. Kim IS, Lee JS. Suppressive effect of arazyme on neutrophil apoptosis in normal and allergic subjects. Biomed Sci Lett. 2014, 20:244-249. https://doi.org/10.15616/BSL.2014.20.4.244
  11. Kim IS, Lee JS. Anti-apoptotic effects of house dust mite, S100A8 and S100A9 on spontaneous apoptosis of neutrophils in coculture with immune cells and in the presence of T helper cytokines. Biomed Sci Lett. 2015, 21:122-125. https://doi.org/10.15616/BSL.2015.21.2.122
  12. Lee JS, Chooi E, Yang EJ, Lee NR, Baek SY, Kim EJ, et al. Induction of the neutrophil migration in normal subjects due to asthmatic bronchoalveolar lavage fluid (BALF). Biomed Sci Lett. 2014, 20:1-6.
  13. Lee JS, Kim IS, Ryu JS, Yun CY. House dust mite, dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human monocytic THP-1 cells. Cytokine. 2008, 42:365-371. https://doi.org/10.1016/j.cyto.2008.03.010
  14. Manz MG, Boettcher S. Emergency granulopoiesis. Nat Rev Immunol. 2014, 14:302-314. https://doi.org/10.1038/nri3660
  15. Rondon C, Campo P, Togias A, Fokkens WJ, Durham SR, Powe DG, et al. Local allergic rhinitis: concept, pathophysiology, and management. J Allergy Clin Immunol. 2012, 129:1460-1467. https://doi.org/10.1016/j.jaci.2012.02.032
  16. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000, 18:217-242. https://doi.org/10.1146/annurev.immunol.18.1.217
  17. Schulz O, Sewell HF, Shakib F. Proteolytic cleavage of CD25, the a subunit of the human T cell interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity. J Exp Med. 1998, 187:271-275. https://doi.org/10.1084/jem.187.2.271
  18. Thomas WR, Smith WA, Hales BJ, Mills KL, O'Brien RM. Characterization and immunobiology of house dust mite allergens. Int Arch Allergy Immunol. 2002, 129:1-18. https://doi.org/10.1159/000065179
  19. Thomas WR, Hales BJ, Smith WA. House dust mite allergens in asthma and allergy. Trends Mol Med. 2010, 16:321-328. https://doi.org/10.1016/j.molmed.2010.04.008
  20. Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol. 2015, 15:271-282. https://doi.org/10.1038/nri3831
  21. Yang EJ, Choi E, Ko J, Kim DH, Lee JS. Differential effect of CCL2 on constitutive neutrophil apoptosis between normal and asthmatic subjects. J Cell Physiol. 2012, 227:2567-2577. https://doi.org/10.1002/jcp.22995

피인용 문헌

  1. Suppressive Effect of Der p 2 on Constitutive Neutrophil Apoptosis by Cytokine Secretion of Normal and Allergic Lymphocytes vol.48, pp.2, 2016, https://doi.org/10.15324/kjcls.2016.48.2.102
  2. S100A8 Induces Secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T Cells vol.22, pp.2, 2015, https://doi.org/10.15616/bsl.2016.22.2.60
  3. House Dust Mite Allergen Inhibits Constitutive Neutrophil Apoptosis by Cytokine Secretion via PAR2/PKCδ/p38 MAPK Pathway in Allergic Lymphocytes vol.48, pp.3, 2015, https://doi.org/10.15324/kjcls.2016.48.3.188
  4. S100A8 and S100A9 Secreted by Allergens in Monocytes Inhibit Spontaneous Apoptosis of Normal and Asthmatic Neutrophils via the Lyn/Akt/ERK Pathway vol.49, pp.2, 2017, https://doi.org/10.15324/kjcls.2017.49.2.128