Use of early passage fetal intestinal epithelial cells in semi-high-throughput screening assays: An approach to identify new innate immune system adjuvants

被引:8
作者
Buckner, Diana [1 ]
Wilson, Suzanne [1 ]
Kurk, Sandra [1 ]
Hardy, Michele [1 ]
Miessner, Nicole [1 ]
Jutila, Mark A. [1 ]
机构
[1] Montana State Univ, Bozeman, MT 59718 USA
关键词
innate adjuvant; epithelial cell; cytokine; mucosa;
D O I
10.1177/1087057106289876
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Innate immune system stimulants (innate adjuvants) offer complementary approaches to vaccines and antimicrobial compounds to increase host resistance to infection. The authors established fetal bovine intestinal epithelial cell (BIEC) cultures to screen natural product and synthetic compound libraries for novel mucosal adjuvants. They showed that BIECs from fetal intestine maintained an in vivo phenotype as reflected in cytokeratin expression, expression of antigens restricted to intestinal enterocytes, and induced interieukin-8 (IL-8) production. BIECs could be infected by and support replication of bovine rotavirus. A semi-high-throughput enzyme-linked immunosorbent assay-based assay that measured IL-8 production by BIECs was established and used to screen commercially available natural compounds for novel adjuvant activity. Five novel hits were identified, demonstrating the utility of the assay for selecting and screening new epithelial cell adjuvants. Although the identified compounds had not previously been shown to induce IL-8 production in epithelial cells, other known functions for 3 of the 5 were consistent with this activity. Statistical analysis of the throughput data demonstrated that the assay is adaptable to a high-throughput format for screening both synthetic and natural product derived compound libraries.
引用
收藏
页码:664 / 671
页数:8
相关论文
共 21 条
[1]   Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents [J].
Baldridge, JR ;
McGowan, P ;
Evans, JT ;
Cluff, C ;
Mossman, S ;
Johnson, D ;
Persing, D .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2004, 4 (07) :1129-1138
[2]   Therapeutic manipulation of the immune system: enhancement of innate and adaptive mucosal immunity [J].
Boyaka, PN ;
Tafaro, A ;
Fischer, R ;
Fujihashi, K ;
Jirillo, E ;
McGhee, JR .
CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (24) :1965-1972
[3]   A STUDY ON NEONATAL CALF DIARRHEA INDUCED BY ROTAVIRUS [J].
CASTRUCCI, G ;
FERRARI, M ;
FRIGERI, F ;
TRALDI, V ;
ANGELILLO, V .
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 1994, 17 (3-4) :321-331
[4]   Ion transport and regulation of respiratory tract fluid output in dogs [J].
Chen, BT ;
Yeates, DB .
JOURNAL OF APPLIED PHYSIOLOGY, 2001, 90 (03) :821-831
[5]   Cantharidin blisters: a technique for investigating leukocyte trafficking and cytokine production at sites of inflammation in humans [J].
Day, RM ;
Harbord, M ;
Forbes, A ;
Segal, AW .
JOURNAL OF IMMUNOLOGICAL METHODS, 2001, 257 (1-2) :213-220
[6]   Innate immune activation as a broad-spectrum biodefense strategy: Prospects and research challenges [J].
Hackett, CJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 112 (04) :686-694
[7]   Shigella and Salmonella:: death as a means of survival [J].
Haimovich, B ;
Venkatesan, MM .
MICROBES AND INFECTION, 2006, 8 (02) :568-577
[8]   IDENTIFICATION OF A HUMAN PERIPHERAL LYMPH-NODE HOMING RECEPTOR - A RAPIDLY DOWN-REGULATED ADHESION MOLECULE [J].
KISHIMOTO, TK ;
JUTILA, MA ;
BUTCHER, EC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (06) :2244-2248
[9]   Amlodipine inhibits the production of cytokines induced by ouabain [J].
Matsumori, A ;
Ono, K ;
Nishio, R ;
Nose, Y ;
Sasayama, S .
CYTOKINE, 2000, 12 (03) :294-297
[10]   Comparison of in vitro models for the prediction of compound absorption across the human intestinal mucosa [J].
Miret, S ;
Abrahamse, L ;
De Groene, EM .
JOURNAL OF BIOMOLECULAR SCREENING, 2004, 9 (07) :598-606