| First Author | Cheng Y | Year | 2017 |
| Journal | Mol Biol Cell | Volume | 28 |
| Issue | 1 | Pages | 201-209 |
| PubMed ID | 27807045 | Mgi Jnum | J:318417 |
| Mgi Id | MGI:6859576 | Doi | 10.1091/mbc.E16-02-0126 |
| Citation | Cheng Y, et al. (2017) HMGB1 translocation and release mediate cigarette smoke-induced pulmonary inflammation in mice through a TLR4/MyD88-dependent signaling pathway. Mol Biol Cell 28(1):201-209 |
| abstractText | We performed studies to determine the role of high-mobility group box 1 (HMGB1) in cigarette smoke (CS)-induced pulmonary inflammation. After mice were exposed to five cigarettes four times a day for 3 d, toll-like receptor 4 (TLR4) expression and TLR4-mediated signaling were significantly up-regulated, and HMGB1 had translocated from the nucleus to the cytoplasm in lung epithelial cells and then been released into the extracellular lung space. On CS exposure, inflammatory cell recruitment and proinflammatory cytokine production were significantly increased in lung tissue and bronchoalveolar lavage, and these effects depended on the TLR4 signaling pathway. HMGB1 inhibition decreased the CS-induced inflammatory response, whereas treatment with exogenous HMGB1 aggravated the damage and increased the phosphorylation of JNK, p38, and IkappaBalpha in the lungs of wild-type mice but not in TLR4-knockout mice. Blockade of TLR4 action or TLR4 knockout significantly inhibited HMGB1-induced proinflammatory cytokine production in mouse tracheal epithelial (MTE) cells and lung tissues. In addition, a MyD88 deficiency inhibited JNK, p38, and IkappaBalpha phosphorylation, and this effect was associated with the suppressed production of TNF-alpha and IL-1beta in MTE cells and lung tissues in response to CS stimulation. Thus HMGB1 activates the NF-kappaB and JNK/p38 pathways through TLR4/MyD88-dependent signaling and induces an inflammatory response in lungs exposed to CS. |
