Next Article in Journal
Molecular Cloning and Characterization of DXS and DXR Genes in the Terpenoid Biosynthetic Pathway of Tripterygium wilfordii
Previous Article in Journal
Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(10), 25502-25515; doi:10.3390/ijms161025502

The Fab Fragment of a Humanized Anti-Toll Like Receptor 4 (TLR4) Monoclonal Antibody Reduces the Lipopolysaccharide Response via TLR4 in Mouse Macrophage

1
Department of Infectious Disease, Anhui Medical University Affiliated with Bayi Clinical College, Hefei 230000, China
2
Institute of Liver Disease, Nanjing Jingdu Hospital, Nanjing 210002, China
3
Department of Microbiology, Huadong Medical Institute of Biotechnology, Nanjing 210002, China
4
Department of Pathology, Key Laboratory of Antibody Technique of the Ministry of Health, NJMU, Nanjing 210029, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Ester Boi
Received: 28 August 2015 / Revised: 24 September 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
(This article belongs to the Section Molecular Recognition)
View Full-Text   |   Download PDF [1268 KB, uploaded 23 October 2015]   |  

Abstract

Lipopolysaccharides (LPS) can induce acute inflammation, sepsis, or chronic inflammatory disorders through the Toll receptor 4 (TLR4) signaling pathway. The TLR4/MD2 (myeloid differentiation protein 2) complex plays a major role in the immune response to LPS. However, there is not a good method to suppress the immune response induced by LPS via this complex in macrophages. In this article, we aimed to evaluate the effects of humanized anti-TLR4 monoclonal antibodies on LPS-induced responses in mouse macrophages. The peritoneal macrophages of mice were incubated with anti-TLR4 monoclonal antibodies and stimulated with LPS. The expression levels of cytokines were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assays. Additionally, activation of various signaling pathways was evaluated by Western blotting. The results showed that the humanized anti-TLR4 monoclonal antibody blocked the inflammatory cytokines expression at both the mRNA and protein level. We also found that the Fab fragment significantly inhibited the nuclear factor kappaB signaling pathway by reducing the phosphorylation of the inhibitor of kappaBalpha and decreasing the translocation of p65, resulting in the suppression of p38, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, and IFN-β regulatory factor 3 phosphorylation. Therefore, our study showed that this humanized anti-TLR4 monoclonal antibody could effectively protect against LPS-induced responses by blocking the TLR4 signaling pathway in mouse peritoneal macrophages. View Full-Text
Keywords: humanized anti-Toll like receptor 4 antibody; Fab fragment; lipopolysaccharide; Toll-like receptor 4 signaling humanized anti-Toll like receptor 4 antibody; Fab fragment; lipopolysaccharide; Toll-like receptor 4 signaling
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cai, B.; Wang, M.; Zhu, X.; Xu, J.; Zheng, W.; Zhang, Y.; Zheng, F.; Feng, Z.; Zhu, J. The Fab Fragment of a Humanized Anti-Toll Like Receptor 4 (TLR4) Monoclonal Antibody Reduces the Lipopolysaccharide Response via TLR4 in Mouse Macrophage. Int. J. Mol. Sci. 2015, 16, 25502-25515.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top