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

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)-B 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-B signaling pathway, and whether it proceeds via the inhibition of the activation of the LXA4 receptor and anti-interleukin (IL)-1 antibodies. Mice with airway inflammation induced by OVA administration were treated with or without a LXA4 receptor agonist, BML-111 and anti-IL-1 antibody. Serum levels of IL-1, IL-4, IL-8 and interferon- (IFN-) were assessed, and levels of IL-1, 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-B in the lungs were analyzed. Expression of TLR2 and MyD88, and activation of NF-B in leukocytes as well as levels of IL-4, IL-6 and IL-8 released from leukocytes exposed to IL-1 were assessed. OVA treatment increased the levels of IL-1, 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-B in the lung. These increments induced by OVA were inhibited by treatment with BML-111 and anti-IL-1 antibodies. Treatment of the leukocytes with BML-111 or TLR2 antibody, or MyD88 or NF-B inhibitor, all blocked the IL-1-triggered production of IL-4, IL-6 and IL-8 and activation of NF-B. Treatment of the leukocytes with BML-111 or TLR2 antibody suppressed IL-1-induced TLR2 and MyD88 expression. The present study therefore suggested that OVA-induced airway inflammation is mediated by the TLR2/MyD88/NF-B pathway. IL-1 has a pivotal role in the airway inflammation and upregulation of the TLR2/MyD88/NF-B pathway induced by OVA. BML-111 and anti-IL-1 antibody restrains the OVA-induced airway inflammation via downregulation of the TLR2/MyD88/NF-B pathway.