title: Cold-inducible RNA-binding protein mediates airway inflammation and mucus hypersecretion through a post-transcriptional regulatory mechanism under cold stress.
abstract: Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects. Similarly, inflammatory cytokine production and MUC5AC secretion were up-regulated in rats following cigarette smoke inhalation. Cold temperature-induced CIRP overexpression and translocation were shown to be dependent on arginine methylation in vitro. CIRP overexpression promoted stress granule (SG) assembly. In the cytoplasm, the stability of pro-inflammatory cytokine mRNAs was increased through specific interactions between CIRP and mediator mRNA 3'-UTRs; these interactions increased the mRNA translation, resulting in MUC5AC overproduction in response to cold stress. Conversely, CIRP silencing and a methyltransferase inhibitor (adenosine dialdehyde) promoted cytokine mRNA degradation and inhibited the inflammatory response and mucus hypersecretion. These findings indicate that cold temperature can induce an airway inflammatory response and excess mucus production via a CIRP-mediated increase in mRNA stability and protein translation.
authors.affiliation: Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing, China. Electronic address: yangjuan110366@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Juan
authors.affiliation: Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Haiqiao
authors.affiliation: Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing, China.
authors.forename: Wenyao
authors.initials: W
authors.lastname: Xie
authors.affiliation: Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Huaping
authors.affiliation: Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiangdong
authors.affiliation: Far Eastern Scientific Center of Physiology and Pathology of Respiration, Siberian Branch, Russian Academy of Medical Sciences, Russian Federation.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.affiliation: Far Eastern Scientific Center of Physiology and Pathology of Respiration, Siberian Branch, Russian Academy of Medical Sciences, Russian Federation.
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D001991:Bronchitis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D058639:Cold-Shock Response / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D055271:Mucin 5AC / Q000096:biosynthesis; D009093:Mucus / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; C491390:CIRBP protein, human; D016207:Cytokines; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016601:RNA-Binding Proteins; D012906:Smoke
keywords: 3′-UTR; Cold stress; Cold-inducible RNA-binding protein; MUC5AC; Post-translational; Pro-inflammatory cytokine; mRNA stability