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  2. Unveiling the mechanisms of trichloroethylene hypersensitivity syndrome: Exploring the role of connexin 43 gap junctions in severe skin damage

Unveiling the mechanisms of trichloroethylene hypersensitivity syndrome: Exploring the role of connexin 43 gap junctions in severe skin damage

  • Food Chem Toxicol. 2024 Mar 13:187:114594. doi: 10.1016/j.fct.2024.114594.
Bo Jiao 1 Haiqin Jiang 2 Shuai Liu 1 Yican Wang 1 Yuanyuan Chen 3 Huawei Duan 1 Yong Niu 1 Meili Shen 1 Hongsheng Wang 2 Yufei Dai 4
Affiliations

Affiliations

  • 1 National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China.
  • 2 Institute of Dermatology, Chinese Academy of Medical Sciences, National Center for STD and Leprosy Control, China CDC, Nanjing, China.
  • 3 China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, 100021, China.
  • 4 National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China; China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, 100021, China. Electronic address: daiyf@chinacdc.cn.
Abstract

Trichloroethylene (TCE), extensively used as an organic solvent in various industrial applications, has been identified as a causative factor in inducing hypersensitivity syndrome (THS). Currently, there is no specific treatment for THS, and most patients experience serious adverse outcomes due to extensive skin damage leading to severe Infection. However, the pathogenesis of THS-associated skin damage remains unclear. This study aims to elucidate the mechanism underlying skin damage from the perspective of intercellular communication and gap junctions in THS. Our results verified that hyperactivation of connexin43 gap junctions, caused by the aberrantly elevated expression of connexin43, triggers a bystander effect that promotes Apoptosis and inflammation in THS via the TNF-TNFRSF1B and mitochondria-associated pathways. Additionally, we identified the gap junction inhibitor Carbenoxolone disodium (CBX) as a promising agent for the treatment of skin damage in THS. CBX protects against inflammatory cell infiltration in the skin and decreases immune cell imbalance in the peripheral blood of THS mice. Furthermore, CBX reduces connexin43 expression, Apoptosis and inflammation in THS mice. The study reveals new insights into the mechanisms underlying TCE-induced skin damage, offering a potential treatment strategy for the development of effective therapies targeting severe dermatitis induced by chemical exposure.

Keywords

Connexin 43 gap junctions; Hypersensitivity syndrome; Trichloroethylene.

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