title: IL-1β maintains the redox balance by regulating glutaredoxin 1 expression during oral carcinogenesis.
abstract: BACKGROUND
  Interleukin-1 beta (IL-1β) is a pleiotropic cancer-inflammation-linked cytokine which has been reported upregulated in many cancers. In our previous study, IL-1β was found to be one of the key node genes during oral malignant transformation, and glutaredoxin 1 (Grx1) was identified as one of the downstream genes of IL-1β in tumor microenvironment. Grx1 is ubiquitous oxidoreductase which is necessary for scavenging reactive oxygen species (ROS) and the intracellular redox balance maintenance.
  
  
  METHODS
  Tissues from different stages of mucosal malignant transformation were obtained from 4NQO-induced rat oral carcinogenesis model and human mucosa for Grx1 expression detection by immunohistochemical staining. The intracellular ROS levels and Grx1 mRNA level of oral squamous carcinoma cell CAL27 were detected after IL-1β treatment with or without pretreatment of IL-1Ra or NAC, respectively. The ROS levels were detected in Leti-si-IL-1β and Leti-si-NC CAL27 cells after IL-1β stimulation. The invasion and migration abilities of CAL27 cells were tested by transwell assay after IL-1β stimulation with or without pretreatment of IL-1Ra.
  
  
  RESULTS
  Grx1 expression was associated with the malignant transformation process in vivo. Exogenous IL-1β upregulated the intracellular ROS level and the expression of Grx1 in CAL27 cells, which could be counteracted by IL-1Ra. The intracellular ROS accumulation induced by exogenous IL-1β was responsible for the Grx1 upregulation. Endogenous IL-1β acted as a switch in regulating the ROS level by modulating Grx1 expression, which was involved in the invasion and migration of OSCC cells.
  
  
  CONCLUSIONS
  IL-1β finely orchestrated the redox balance during carcinogenesis by modulating Grx1 expression.
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Qianshu
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Oral Medicine, Hospital of Stomatology, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D054477:Glutaredoxins / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species
keywords: Grx1; IL-1β; oral squamous cell carcinoma; reactive oxygen species; redox balance