DOI QR코드

DOI QR Code

S100A8 and S100A9 Secreted by Allergens in Monocytes Inhibit Spontaneous Apoptosis of Normal and Asthmatic Neutrophils via the Lyn/Akt/ERK Pathway

단구에서 분비되는 S100A8과 S100A9의 Lyn/Akt/ERK 경로를 통한 정상인과 천식질환 호중구의 세포고사 억제 효과

  • Kim, In Sik (Department of Biomedical Laboratory Science, School of Medicine, Eulji University) ;
  • Lee, Ji-Sook (Department of Clinical Laboratory Science, Wonkwang Health Science University)
  • 김인식 (을지대학교 대전캠퍼스 임상병리학과) ;
  • 이지숙 (원광보건대학교 임상병리과)
  • Received : 2017.04.13
  • Accepted : 2017.05.29
  • Published : 2017.06.30

Abstract

Der p 1 and Der p 2 are essential allergens of house dust mite associated with the development of asthma. In the present study, we examined whether Der p 1 and Der p 2 induce a release of S100A8 and S100A9 in monocytes, which are involved in the regulatory mechanism of neutrophil apoptosis. We found that Der p 1 and Der p 2 significantly increased the secretion of S100A8 and S100A9 in normal monocytes. Moreover, S100A8 and S100A9 strongly suppressed the spontaneous apoptosis of normal and asthmatic neutrophils. The inhibitory effect of S100A9 was stronger than that of S100A8, and asthmatic neutrophils showed a higher inhibitory effect than normal neutrophils. S100A8 and S100A9 induced activation of Lyn, Akt, and ERK in a time-dependent manner. These findings elucidate the roles of Der p 1 and Der p 2 in the interaction between monocytes and neutrophils, as well as contributing to our knowledge of the pathogenesis of allergic diseases.

Der p 1과 Der p 2는 알레르기 질환과 관련된 집먼지 진드기의 핵심적인 알러젠이다. 본 연구에서는 Der p 1과 Der p 2가 단구에서 S100A8과 S10A9을 분비시키는지를 확인하였고, 분비된 S100A8과 S10A9이 호중구의 세포고사 조절기전에 작용하는지를 연구하였다. Der p 1과 Der p 2는 정상인의 단구에서 S100A8과 S10A9을 유의하게 증가시켰고, S100A8과 S10A9은 정상인과 알레르기 질환 호중구의 자발적 세포고사를 억제 시켰다. 호중구의 Lyn, Akt, ERK는 S100A8과 S10A9을 시간별로 처리하였을 때 활성화하였다. 본 연구를 통하여 단구와 호중구에서 Der p 1과 Der p 2의 역할을 규명하였고, 나아가 관련된 알레르기 병인기전을 이해하는데 유용할 것이다.

Keywords

References

  1. Hogate ST. Pathogenesis of asthma. Clin Exp Allergy. 2008;38(6):872-897. https://doi.org/10.1111/j.1365-2222.2008.02971.x
  2. Gaffin, JM, Phipatanakul W. The role of indoor allergens in the development of asthma. Curr Opin Allergy Clin Immunol. 2009;9(2):128-135. https://doi.org/10.1097/ACI.0b013e32832678b0
  3. 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
  4. Kim IS, Lee NR, Lee JS. Der p 1 inhibits spontaneous neutrophil apoptosis by cytokine secretion of normal and allergic lymphocytes. Korean J Clin Lab Sci. 2015;47:230-236. https://doi.org/10.15324/kjcls.2015.47.4.230
  5. 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-${\gamma}$. Eur J Immunol. 2001;31(4):1211-1216. https://doi.org/10.1002/1521-4141(200104)31:4<1211::AID-IMMU1211>3.0.CO;2-R
  6. 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(10):1468-1475. https://doi.org/10.1046/j.1365-2745.2002.01504.x
  7. Yu SJ, Liao EC, Sheu ML, Chang DT, Tsai JJ. Cell-penetrating peptide derived from human eosinophil cationic protein inhibits mite allergen Der p 2 induced inflammasome activation. PLoS One. 2015;10:e0129187. https://doi.org/10.1371/journal.pone.0129187
  8. Tsai J1, Shen HD, Chua KY. Purification of group 2 Dermatophagoides pteronyssinus allergen and prevalence of its specific IgE in asthmatics. Int Arch Allergy Immunol. 2000;121(3):205-210. https://doi.org/10.1159/000024318
  9. Goyette J, Geczy CL. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids. 2011;41(4):821-842. https://doi.org/10.1007/s00726-010-0528-0
  10. Kerkhoff Cl, Voss A, Scholzen TE, Averill MM, Zanker KS, Bornfeldt KE. Novel Insights into the role of S100A8/A9 in skin biology. Exp Dermatol. 2012;21(11):822-826. https://doi.org/10.1111/j.1600-0625.2012.01571.x
  11. Nam AR, Kim DH, Kim MJ, Lee JS, Yang SJ, Kim IS. S100A8 induces secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T cells. Biomed Sci Lett. 2016;22:60-64. https://doi.org/10.15616/BSL.2016.22.2.60
  12. Gebhardt C, Nemeth J, Angel P, Hess J. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol. 2006;72(11):1622-1631. https://doi.org/10.1016/j.bcp.2006.05.017
  13. Chen B, Miller AL, Rebelatto M, Brewah Y, Rowe DC, Clarke L, et al. S100A9 induced inflammatory responses are mediated by distinct damage associated molecular patterns (DAMP) receptors in vitro and in vivo. PLoS One. 2015;10:e0115828. https://doi.org/10.1371/journal.pone.0115828
  14. 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
  15. Lee NR, Baek SY, Gu A, Kim DH, Kim SY, Lee JS, et al. House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes. Immunol Res. 2016;64(1):123-132. https://doi.org/10.1007/s12026-015-8730-5
  16. Kim DH, Choi E, Lee JS, Lee NR, Baek SY, Gu A, et al. House dust mite allergen regulates constitutive apoptosis of normal and athmatic neutrophils via Toll-Like Receptor 4. PLoS One. 2015;10:e0125983 https://doi.org/10.1371/journal.pone.0125983
  17. 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.
  18. Thomas WR, Hales BJ, Smith WA. House dust mite allergens in asthma and allergy. Trends Mol Med. 2010;16(17):321-328. https://doi.org/10.1016/j.molmed.2010.04.008
  19. Kim IS, Lee NR, Lee JS. Suppressive effect of Der p 2 on constitutive neutrophil apoptosis by cytokine secretion of normal and allergic lymphocytes. Korean J Clin Lab Sci. 2016;48:102-108. https://doi.org/10.15324/kjcls.2016.48.2.102
  20. 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.
  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(6):2567-2577. https://doi.org/10.1002/jcp.22995
  22. Sun Z, Dragon S, Becker A, Gounni AS. Leptin inhibits neutrophil apoptosis in children via $RK/NF-{\kappa}B-dependent$ pathways. PLoS One. 2013;8(1):e55249. https://doi.org/10.1371/journal.pone.0055249

Cited by

  1. The Pro-apoptotic Effects of S100A8 and S100A9 in Human Monocytic Leukemia Cells, THP-1 vol.24, pp.2, 2018, https://doi.org/10.15616/bsl.2018.24.2.134
  2. Metformin or α-Lipoic Acid Attenuate Inflammatory Response and NLRP3 Inflammasome in BV-2 Microglial Cells vol.52, pp.3, 2017, https://doi.org/10.15324/kjcls.2020.52.3.253
  3. Inhibitory Effect of S100A8 on Neutrophil Apoptosis by Cytokine Release of Normal and Allergic Monocytes vol.26, pp.3, 2017, https://doi.org/10.15616/bsl.2020.26.3.226