Roles of lipoxin A4 receptor activation and anti-interleukin-1β antibody on the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-κB pathway in airway inflammation induced by ovalbumin

Kong,Xia; Wu,Sheng‑Hua; Zhang,Li; Chen,Xiao‑Qing

doi:10.3892/mmr.2015.3443

Roles of lipoxin A4 receptor activation and anti-interleukin-1β antibody on the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-κB pathway in airway inflammation induced by ovalbumin

Authors:
- Xia Kong
- Sheng‑Hua Wu
- Li Zhang
- Xiao‑Qing Chen
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Affiliations: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
Published online on: March 5, 2015 https://doi.org/10.3892/mmr.2015.3443
Pages: 895-904
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Previous studies investigating the role of toll‑like receptors (TLRs) in asthma have been inconclusive. It has remained elusive whether the toll‑like receptors (TLR2)/mycloid differentiation factor 88 (MyD88)/nuclear factor (NF)‑κB signaling pathway is involved in lipoxin A4 (LXA4)‑induced protection against asthma. Therefore, the present study investigated whether ovalbumin (OVA)‑induced airway inflammation is mediated by upregulation of the TLR2/MyD88/NF‑κB signaling pathway, and whether it proceeds via the inhibition of the activation of the LXA4 receptor and anti‑interleukin (IL)‑1β antibodies. Mice with airway inflammation induced by OVA administration were treated with or without a LXA4 receptor agonist, BML‑111 and anti‑IL‑1β antibody. Serum levels of IL‑1β, IL‑4, IL‑8 and interferon‑γ (IFN‑γ) were assessed, and levels of IL‑1β, IL‑4, IL‑8 and OVA‑immunoglobulin (Ig)E, as well as leukocyte counts in the bronchoalveolar lavage fluid (BALF) were measured. Pathological features and expression of TLR2, MyD88 and NF‑κB in the lungs were analyzed. Expression of TLR2 and MyD88, and activation of NF‑κB in leukocytes as well as levels of IL‑4, IL‑6 and IL‑8 released from leukocytes exposed to IL‑1β were assessed. OVA treatment increased the levels of IL‑1β, IL‑4 and IL‑8 in the serum and BLAF, the number of leukocytes and the levels of OVA‑IgE in the BALF, the expression of TLR2 and MyD88, and the activation of NF‑κB in the lung. These increments induced by OVA were inhibited by treatment with BML‑111 and anti‑IL‑1β antibodies. Treatment of the leukocytes with BML‑111 or TLR2 antibody, or MyD88 or NF‑κB inhibitor, all blocked the IL‑1β‑triggered production of IL‑4, IL‑6 and IL‑8 and activation of NF‑κB. Treatment of the leukocytes with BML‑111 or TLR2 antibody suppressed IL‑1β‑induced TLR2 and MyD88 expression. The present study therefore suggested that OVA‑induced airway inflammation is mediated by the TLR2/MyD88/NF‑κB pathway. IL‑1β has a pivotal role in the airway inflammation and upregulation of the TLR2/MyD88/NF‑κB pathway induced by OVA. BML‑111 and anti‑IL‑1β antibody restrains the OVA‑induced airway inflammation via downregulation of the TLR2/MyD88/NF‑κB pathway.

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