title: Protective Effect of an Antibody against Specific Extracellular Domain of TLR2 on Agonists-Driven Inflammatory and Allergic Response.
abstract: Specific blocking strategies of TLR2-mediated inflammatory signaling and hypersensitivity reactions may offer novel therapeutic strategies to prevent a variety of diseases. In this study, we investigated the blocking effects of a new anti-TLR2 antibody anti-T20 against a 20 mer peptide T20 located in the extracellular specific domain of mouse TLR2. In addition, the effects of the anti-T20 in vitro, measuring the inhibition of the IL-6 and TNF-α production in response to PGN, LTA, and Pam3CSK4-stimulated RAW264.7 cells, were determined. In vivo, the effects of anti-T20 on a lethal anaphylaxis model using PGN-challenged OVA allergic mice, including the rectal temperature and mortality, and serum levels of TNF-α, IL-6, and LTC4 were assayed. The results showed that anti-T20 specifically bound to TLR2 and significantly inhibited PGN, LTA, and Pam3CSK4-driven TNF-α and IL-6 production by RAW264.7 cells. Also, anti-T20 protected OVA allergic mice from PGN-induced lethal anaphylaxis, and the serum levels of TNF-α, IL-6, and LTC4 of anti-T20 treated PGN-challenged OVA allergic mice were decreased as compared to isotype control of anti-T20 treated mice. In summary, this study produced a new antibody against the specific extracellular domain of TLR2 which has protective effect on TLR2 agonists-driven inflammatory and allergic response.
authors.affiliation: Department of Burns and Plastics, The People's Hospital of Anyang City, Anyang, Henan 455000, China.
authors.forename: Tianwu
authors.initials: T
authors.lastname: Guo
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Peng
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Qiaofen
authors.initials: Q
authors.lastname: Lan
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Huanjin
authors.initials: H
authors.lastname: Liao
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: The Institute of Nephrology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Pan
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D000077560:Enfuvirtide; D005786:Gene Expression Regulation / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D017997:Leukotriene C4 / Q000096:biosynthesis; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D000072417:Protein Domains / Q000235:genetics; D000067996:RAW 264.7 Cells; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015700:HIV Envelope Protein gp41; D015850:Interleukin-6; D010446:Peptide Fragments; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000077560:Enfuvirtide; D017997:Leukotriene C4