title: Autophagy facilitates cytokine-induced ICAM-1 expression.
abstract: ICAM-1 can be induced by inflammatory cytokines such as IFN-γ and TNF-α. This study investigated whether autophagy regulates ICAM-1 given that autophagy facilitates signaling of these two cytokines. Exogenous IFN-γ induced ICAM-1 in human lung epithelial A549 cells carrying wild type p53, a transcription factor reported for ICAM-1, but not in PC14PE6/AS2 (AS2) cells carrying mutated p53. However, IFN-γ also induced ICAM-1 in A549 cells with short hairpin RNA-silenced p53. No changes in IFN-γ receptor expression were observed in AS2 cells, but IFN-γ-activated Jak2/STAT1/IFN regulatory factor 1 was markedly decreased. In AS2 cells, increased levels of reactive oxygen species induced the activation of Src homology domain-containing phosphatase 2 (SHP2), while SHP2 was essential for IFN-γ resistance. AS2 cells showed autophagy resistance, and the manipulation of the autophagy pathway altered IFN-γ resistance. Aberrant Bcl-2 expression and mammalian target of rapamycin activation contributed to both autophagy resistance and IFN-γ resistance. Autophagy, but not p53, also modulated TNF-α-induced NF-κB activation and ICAM-1 expression. Inhibiting autophagy decreased the adhesion of human monocytic U937 cells to IFN-γ-treated A549 cells. These results demonstrated that IFN-γ and TNF-α induced ICAM-1 expression through a common pathway that was regulated by autophagy, but not p53.
authors.affiliation: 1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chi-Yun
authors.initials: CY
authors.lastname: Wang
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Chiang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Tseng
authors.forename: Shun-Yi
authors.initials: SY
authors.lastname: Chien
authors.forename: Yi-Jui
authors.initials: YJ
authors.lastname: Chuang
authors.forename: Tsan-Tzu
authors.initials: TT
authors.lastname: Yang
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Choi
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000276:immunology; D020545:Respiratory Mucosa / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: Autophagy; ICAM-1; IFN-γ; TNF-α; cytokine