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알레르기 림프구에서 집먼지진드기 알러젠의 PAR2/PKCδ/p38 MAPK 경로를 통한 사이토카인 증가는 호중구의 세포고사를 억제시킨다

House Dust Mite Allergen Inhibits Constitutive Neutrophil Apoptosis by Cytokine Secretion via PAR2/PKCδ/p38 MAPK Pathway in Allergic Lymphocytes

  • 이나래 (을지대학교 대전캠퍼스 임상병리학과) ;
  • 이지숙 (원광보건대학교 임상병리과) ;
  • 김인식 (을지대학교 대전캠퍼스 임상병리학과)
  • 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) ;
  • Kim, In Sik (Department of Biomedical Laboratory Science, School of Medicine, Eulji University)
  • 투고 : 2016.05.31
  • 심사 : 2016.06.28
  • 발행 : 2016.09.30

초록

본 연구에서는 집먼지 진드기 추출물은 호중구에 단독으로 작용하는 것보다, 림프구와 호중구의 공동배양에서 호중구의 세포고사를 더 억제시켰다. 집먼지 진드기는 알레르기 질환의 림프구에서 IL-6, IL-8, MCP-1, GM-CSF의 분비를 증가시켰다. 집먼지 진드기에 의해 증가된 사이토카인은 protein kinase C ${\delta}$의 억제제인 rottlerin과 p38 MAPK의 억제제인 SB202190에 의해서 감소하였다. 집먼지 진드기에 의해 활성화된 p38 MAPK은 protease-activated receptor (PAR2)의 억제제, rottlerin, SB202190에 의해서 억제되었다. Serine protease 억제제인 aprotinin과 cysteine protease 억제제인 E64은 림프구의 사이토카인의 증가와 관련이 없었다. 또한 집먼지 진드기에 의해 증가된 사이토카인의 변화는 천식과 알레르기 비염 환자에서 차이가 없었다. 림프구에서 집먼지진드기에 의해서 분비되는 분자들은 호중구의 유주운동을 억제시켰다. 본 연구를 통하여 집먼지진드기에 의해 유발되는 알레르기 질환의 병인기전을 규명하는데 유용한 결과가 될 것이다.

Neutrophils and lymphocytes are essential inflammatory cells in the pathogenesis of allergy. In this study, we evaluated the role of house dust mite (HDM) in the interaction between allergic lymphocytes and neutrophils. The extract of Dermatophagoides pteronissinus (DP) showed a stronger anti-apoptotic impact on neutrophil apoptosis in the coculture of allergic neutrophils with allergic lymphocytes when compared with that in allergic neutrophils alone. DP increased IL-6, IL-8, MCP-1, and GM-CSF in allergic lymphocytes, and the increased cytokines were inhibited by rottlerin-an inhibitor of the protein kinase C (PKC) ${\delta}$, as well as by SB202190-a p38 MAPK inhibitor. DP activated p38 MAPK in a time-dependent manner. The activation of p38 MAPK was suppressed by PAR2i, which is a protease-activated receptor (PAR) 2 inhibitor, and rottlerin. Both aprotinin-a serine protease inhibitor-and E64-a cysteine protease inhibitor-were not effective on cytokine secretion of lymphocytes. These results, despite increased cytokines in allergic lymphocytes via DP, did not show any differences between asthma and allergic rhinitis. Molecules, including cytokines, released by DP in lymphocytes inhibited the migration of neutrophils. This finding may further elucidate the pathogenic mechanism of allergic diseases due to HDM.

키워드

참고문헌

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피인용 문헌

  1. 비침습적 피부장벽단백질 측정을 통한 아토피 피부염의 진단 및 유용성 vol.49, pp.4, 2017, https://doi.org/10.15324/kjcls.2017.49.4.395