title: A novel hypothesis: up-regulation of HO-1 by activation of PPARγ inhibits HMGB1-RAGE signaling pathway and ameliorates the development of ALI/ARDS.
abstract: Suppression of inflammation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) by activation of peroxisome proliferator-activated receptor (PPAR)-γ has been well demonstrated in animal model studies. However, the molecular mechanisms underlying this effect remain largely unknown. The induction of heme oxygenase-1 (HO-1) exerts antioxidant, anti-apoptotic, and immunomodulatory functions in various situations. Recent studies have indicated that activation of PPARγ induces expression of HO-1, suggesting that HO-1 is a downstream target of PPARγ. Meanwhile, study has shown that activation of PPARγ ameliorates inflammatory response of cells by inhibiting high mobility group box 1 (HMGB1) release. In pulmonary system, binding of HMGB1 to its receptor for advanced glycation end-products (RAGE) triggers the production of pro-inflammatory cytokines, chemokines, adhesion molecules and reactive oxygen species, promoting the development of ALI/ARDS. Based on the recent findings that induction of HO-1 protects tissues and cells from extracellular stress by reducing HMGB1 production, we propose the hypothesis that HO-1 may mediate the protective effects of PPARγ on inhibition of HMGB1-RAGE signaling pathway to attenuate the development of ALI/ARDS.
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, People's Republic of China.
authors.forename: Guizuo
authors.initials: G
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinming
authors.initials: X
authors.lastname: Xie
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Shaojun
authors.initials: S
authors.lastname: Li
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
keywords: Peroxisome proliferator-activated receptor (PPAR)-γ; acute lung injury/acute respiratory distress syndrome (ALI/ARDS); heme oxygenase-1 (HO-1); high mobility group box 1 (HMGB1); receptor for advanced glycation end-products (RAGE)