Polymyxin B Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via TLR4-Myd88-IL-6 Pathway

被引：13

作者：

Cheng, Ying ^{[1
]}

Du, Jicong ^{[1
]}

Han, Jiaqi ^{[1
]}

Sun, Weimin ^{[2
,3
]}

Gao, Fu ^{[1
]}

Zhang, Pei ^{[1
]}

Zhao, Hainan ^{[1
]}

Chen, Ming ^{[1
]}

Wang, Jianing ^{[1
]}

Wang, Mingyu ^{[1
]}

Dong, Suhe ^{[1
]}

Sun, Ding ^{[1
]}

Zhang, Yandong ^{[4
]}

Cui, Jianguo ^{[1
]}

Cai, Jianming ^{[1
]}

Liu, Cong ^{[1
]}

机构：

[1] Second Mil Med Univ, Fac Naval Med, Dept Radiat Med, Shanghai, Peoples R China

[2] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai, Peoples R China

[3] Second Mil Med Univ, Inst Immunol, Shanghai, Peoples R China

[4] Nanjing Univ, Model Anim Res Ctr, Nanjing, Jiangsu, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 42卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Polymyxin B; LPS; Radiation; TLR4; Myd88; IL-6; TOLL-LIKE RECEPTORS; INFLAMMATORY RESPONSE SYNDROME; COLONY-STIMULATING FACTOR; INNATE IMMUNITY; HUMAN MONOCYTES; DOWN-REGULATION; TNF-ALPHA; CELLS; LIPOPOLYSACCHARIDE; ENDOTOXIN;

D O I：

10.1159/000478767

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Polymyxin B (PMB) is a cyclic cationic polypeptide antibiotic widely used to counteract the effects of endotoxin contamination, both in vitro and in vivo. Lipopolysaccharide (LPS) is an endotoxin that acts as a radiation protection factor. In this study, we focus on the role of PMB in LPS-induced and radiation-induced mortality in mice. Methods: Mice received total-body radiation or were pretreated by LPS or PMB, and the survival of mice was recorded. Elisa were used to detect the cytokines levels. Results: PMB decreased LPS-induced, but increased radiation-induced mortality in mice. Moreover, PMB could block the LPS-induced radioprotective effect. The ELISA and gene knock-out experiments indicated that PMB reduces TNF-alpha level to block LPS-induced mortality in mice, and inhibits IL-6, G-CSF and IL-10 to increase radiation-induced mortality via the TLR4-Myd88-IL-6 pathway. Conclusions: Our study revealed a role of PMB in LPS-induced endotoxemia and radiation exposure. We infer that the TLR4-Myd88-IL-6 pathway may play a crucial role in the process. (C) 2017 The Author(s) Published by S. Karger AG, Basel

引用

页码：1120 / 1126

页数：7

共 36 条

[1] Toll-like receptors and innate immunity [J].

Akira, S .

ADVANCES IN IMMUNOLOGY, VOL 78, 2001, 78 :1-56

[2] Coordinating TLR-activated signaling pathways in cells of the immune system [J].

Banerjee, Ashish ;

Gerondakis, Steve .

IMMUNOLOGY AND CELL BIOLOGY, 2007, 85 (06) :420-424

[3] ENDOTOXEMIA AND RELEASE OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1-ALPHA IN ACUTE HEATSTROKE [J].

BOUCHAMA, A ;

PARHAR, RS ;

ELYAZIGI, A ;

SHETH, K ;

ALSEDAIRY, S .

JOURNAL OF APPLIED PHYSIOLOGY, 1991, 70 (06) :2640-2644

[4] Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome [J].

Child, NJA ;

Yang, IA ;

Pulletz, MCK ;

de Courcy-Golder, K ;

Andrews, AL ;

Pappachan, VJ ;

Holloway, JW .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2003, 31 :652-653

[5] Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock The EUPHAS Randomized Controlled Trial [J].

Cruz, Dinna N. ;

Antonelli, Massimo ;

Fumagalli, Roberto ;

Foltran, Francesca ;

Brienza, Nicola ;

Donati, Abele ;

Malcangi, Vincenzo ;

Petrini, Flavia ;

Volta, Giada ;

Pallavicini, Franco M. Bobbio ;

Rottoli, Federica ;

Giunta, Francesco ;

Ronco, Claudio .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 301 (23) :2445-2452

[6] THE INHIBITORY EFFECT OF POLYMYXIN-B ON ENDOTOXIN-INDUCED ENDOGENOUS PYROGEN PRODUCTION [J].

DUFF, GW ;

ATKINS, E .

JOURNAL OF IMMUNOLOGICAL METHODS, 1982, 52 (03) :333-340

[7] TNF-α induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway [J].

Dumitru, CD ;

Ceci, JD ;

Tsatsanis, C ;

Kontoyiannis, D ;

Stamatakis, K ;

Lin, JH ;

Patriotis, C ;

Jenkins, NA ;

Copeland, NG ;

Kollias, G ;

Tsichlis, PN .

CELL, 2000, 103 (07) :1071-1083

[8] Polymyxin B sulfate and colistin: Old antibiotics for emerging multiresistant gram-negative bacteria [J].

Evans, ME ;

Feola, DJ ;

Rapp, RP .

ANNALS OF PHARMACOTHERAPY, 1999, 33 (09) :960-967

[9] Impact of p38 MAP Kinase Inhibitors on LPS-Induced Release of TNF-α in Whole Blood and Primary Cells from Different Species [J].

Fehr, Sarah ;

Unger, Anke ;

Schaeffeler, Elke ;

Herrmann, Sonja ;

Laufer, Stefan ;

Schwab, Matthias ;

Albrecht, Wofgang .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 36 (06) :2237-2249

[10] Contemporary assessment of antimicrobial susceptibility testing methods for polymyxin B and colistin: Review of available interpretative criteria and quality control guidelines [J].

Gales, AC ;

Reis, AO ;

Jones, RN .

JOURNAL OF CLINICAL MICROBIOLOGY, 2001, 39 (01) :183-190

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