Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is characterized by low platelet count. Glucocorticoids (GCs) resistance is a great challenge in the treatment of ITP. P-glycoprotein (P-gp) is a widely studied protein, which is associated with drug resistance. However, in ITP, the functional activity and immune regulation mechanism of P-gp remain uncertain. In this study, we evaluated the expression and functional activity of P-gp in different lymphocyte subsets, explored the correlation between P-gp function and GCs resistance and investigated the role of P-gp in ITP pathogenesis. Results indicated that the functional activity and mRNA level of P-gp were significantly higher in GCs-nonresponsive patients than in GCs-responsive patients with ITP. However, these differences in P-gp were only significant in CD8+T cells. P-gp function was related to disease activity rather than GCs therapy. P-gp was involved in secreting granzyme B and perforin, maintaining autoreactive lymphocytes survival and enhancing autologous platelets lysis in ITP. In conclusion, over-functional P-gp might play an important role in the pathogenesis of ITP and induce GCs resistance in nonresponsive ITP patients. The blockage of P-gp could be a promising therapeutic approach for GCs-resistant patients with ITP.
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Wenjie
W
Liu
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Huiyuan
H
Li
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Donglei
D
Zhang
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Mingen
M
Lv
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Yang
Y
Li
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Yating
Y
Hao
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Yunfei
Y
Chen
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Xiaofan
X
Liu
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Feng
F
Xue
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Lei
L
Zhang
a State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin , China.
Renchi
R
Yang
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D017209:Apoptosis; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D016207:Cytokines; D005938:Glucocorticoids; D012333:RNA, Messenger
CD8+ T cells; P-glycoprotein; apoptosis; cytokine; drug resistance