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Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice

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Abstract

We studied the effects of high mobility group box chromosomal protein 1 (HMGB1) and toll-like receptor (TLR4) in diisonoyl phthalate (DINP)-induced asthma. Mice with DINP-induced asthma were treated with a TLR4-signaling inhibitor or anti-HMGB1 antibody, and various markers of asthma were measured 24 h later. DINP increased airway hyperresponsiveness, numbers of cells in BALF, numbers of inflammatory cells (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils) in blood, mucus production, pulmonary fibrosis, Th2 type cytokine levels in BALF, and lung cell apoptosis. On the other hand, administrations of TLR4-signaling inhibitors (TAK-242) or anti-HMGB1 antibodies to a mouse model of DINP-induced asthma reduced biological markers of asthma. These results show TLR4 and HMGB1 both contribute to DINP-induced asthma, and that the inhibitions of TLR4 or HMGB1 offer potential means of treating asthma induced by phthalates like DINP.

Graphical abstract: Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice

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Publication details

The article was received on 25 Feb 2019, accepted on 17 Jun 2019 and first published on 18 Jun 2019


Article type: Paper
DOI: 10.1039/C9TX00048H
Toxicol. Res., 2019, Advance Article

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    Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice

    Y. Hwang, Y. Lee, M. Paik and S. Yee, Toxicol. Res., 2019, Advance Article , DOI: 10.1039/C9TX00048H

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