Role of Translationally Controlled Tumor Protein in Chronic Spontaneous Urticaria : Translationally Controlled Tumor Protein in Chronic Spontaneous Urticaria
만성 자발성 두드러기의 병인기전에서 TCTP의 역할
- 주제(키워드) Translationally Controlled Tumor Protein , Chronic spontaneous urticaria , autoimmunity
- 발행기관 아주대학교
- 지도교수 Hae-Sim Park
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028577
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Background and objectives: Translationally controlled tumor protein (TCTP) is widely expressed as housekeeping protein that has various intracellular and extracellular functions including its ability to activate mast cells. Extracellular TCTP has been found in nasal, bronchoalveolar lavage and skin blister fluids and exhibits the capacity to induce histamine release from basophils, suggesting that TCTP plays a role in allergic diseases including asthma, atopic dermatitis and urticaria. Dimerization of TCTP is important for its cytokine-like activity, therefore, we hypothesized that the dimerized TCTP may have an important role by inducing histamine and other mediator release, which may drive development of chronic spontaneous urticaria (CSU) symptoms. Materials and Methods: One hundred sixteen CSU patients and 70 healthy normal controls (NCs) were enrolled at Ajou University Medical Center, Suwon, South Korea. Serum TCTP levels of study subjects were measured by ELISA and compared according to other CSU-related clinical parameters. Basophil activation test (BAT) was performed by measuring CD203c expression on peripheral basophils from CSU patients. In vitro, β-hexosaminidase release from human mast cell line, monomeric and dimeric TCTP stimulated LAD-2 mast cells was evaluated. Western blot (WB) analysis was performed to detect dimeric TCTP from sera of CSU patients and NCs in non-reducing condition. Rapid dot-blot immunoassay was used for measuring the level of IgG to high affinity Fc epsilon receptor I alpha subunit (FcεRIα) level in serum of CSU patients and NCs. Results: There was no difference between serum levels of TCTP in CSU patients and NCs. The intensity of dimeric TCTP on WB was visually stronger in CSU patients than in NCs. Severe CSU patients had higher serum TCTP levels (P=0.049) and those having IgG positivity to FcɛRIα (P=0.038). Serum TCTP was significantly positive correlated with eosinophil cationic protein levels (Spearman’s rho 0.341, P=0.001). Both basophil and mast cell degranulation were significantly increased after the stimulation with dimeric TCTP, but, not with monomic TCTP. Conclusion: The capability of TCTP to activate basophils and mast cells is dependent on its dimerization process, suggesting that the inhibition of TCTP dimerization might have therapeutic benefit for CSU. Association of TCTP levels with the presence of IgG to FcεRIα autoantibody indicating that autoimmune mechanisms of CSU which may related to its dimerization.
more목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Clinical characteristics of the study subjects 4
B. Evaluation of clinical parameters of CSU patients 5
C. Measurement of TCTP in sera of study subjects 6
D. Purification of recombinant TCTP protein 7
E. Western blotting for detecting the dimerized TCTP in sera from CSU patients and NCs 8
F. Basophil activation test 8
G. Measurement of ß-hexosaminidase release from LAD-2 cells 9
H. Statistical analysis 10
III. RESULTS 12
A. Clinical characteristics of study subjects 12
B. Serum TCTP levels in CSU patients and NCs 12
C. Correlation of serum TCTP levels with clinical characteristics of chronic spontaneous urticaria 14
D. Effects of TCTP on basophil activation 21
E. β-hexosaminidase release from LAD2 cells upon the stimulation with TCTP 22
IV. DISCUSSION 24
V. CONCLUSION 28
REFERENCES 29
