Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

Ho Jin Sung; Sooho Choi; Ji Won Lee; Chang Youp Ok; Yoe Sik Bae; Yun Hee Kim; Weontae Lee; Kyun Heo; In Hoo Kim

doi:10.1016/j.biomaterials.2013.09.107

Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

Ho Jin Sung, Sooho Choi, Ji Won Lee, Chang Youp Ok, Yoe Sik Bae, Yun Hee Kim, Weontae Lee, Kyun Heo, In Hoo Kim

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

Abstract

Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated K_D of 1.72pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca²⁺ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.

Original language	English
Pages (from-to)	578-589
Number of pages	12
Journal	Biomaterials
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.biomaterials.2013.09.107
Publication status	Published - 2014

Bibliographical note

Funding Information:
This work was supported by research grants from the National Cancer Center Grant ( NCC1210330 ).

All Science Journal Classification (ASJC) codes

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.biomaterials.2013.09.107

Cite this

@article{c90940f9bdfa43c78f63f703c191d1f7,

title = "Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8",

abstract = "Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated KD of 1.72pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca2+ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.",

author = "Sung, {Ho Jin} and Sooho Choi and Lee, {Ji Won} and Ok, {Chang Youp} and Bae, {Yoe Sik} and Kim, {Yun Hee} and Weontae Lee and Kyun Heo and Kim, {In Hoo}",

note = "Funding Information: This work was supported by research grants from the National Cancer Center Grant ( NCC1210330 ). ",

year = "2014",

doi = "10.1016/j.biomaterials.2013.09.107",

language = "English",

volume = "35",

pages = "578--589",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "1",

}

TY - JOUR

T1 - Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

AU - Sung, Ho Jin

AU - Choi, Sooho

AU - Lee, Ji Won

AU - Ok, Chang Youp

AU - Bae, Yoe Sik

AU - Kim, Yun Hee

AU - Lee, Weontae

AU - Heo, Kyun

AU - Kim, In Hoo

N1 - Funding Information: This work was supported by research grants from the National Cancer Center Grant ( NCC1210330 ).

PY - 2014

Y1 - 2014

N2 - Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated KD of 1.72pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca2+ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.

AB - Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis of several neutrophil-infiltrating chronic inflammatory diseases. In the current study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity and affinity, yielding an estimated KD of 1.72pM. NMR data revealed that the residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that can modulate multiple biological activities of IL-8 in human neutrophils, including migration, intracellular signaling, and intracellular Ca2+ mobilization. Our results suggest that the 8A-35 aptamer has great potential to be a lead structure in the development of effective therapeutic agents against inflammatory diseases.

UR - http://www.scopus.com/inward/record.url?scp=84887017919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887017919&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2013.09.107

DO - 10.1016/j.biomaterials.2013.09.107

M3 - Article

C2 - 24129312

AN - SCOPUS:84887017919

SN - 0142-9612

VL - 35

SP - 578

EP - 589

JO - Biomaterials

JF - Biomaterials

IS - 1

ER -

Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this