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Transcriptomic analysis reveals that IL-1R8/Sigirr is a novel macrophage migration regulator and suppresses macrophage proliferation through p38 MAPK signaling pathway - 11/02/20

Doi : 10.1016/j.biopha.2020.109846 
Jing Guo a, b, d, Xiangwen Zhan b, c, e, Guiying Xu a, ⁎ , Chuanbin Mao d, ⁎ , Rongfei Wei b, c, e, ⁎
a Beijing Municipal Key Laboratory of Advanced Energy Materials and Technology, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China 
b Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences ＆ Comparative Medical Center, Peking Union Medical College, Beijing 100021, China 
c Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China 
d Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019-5300, USA 
e Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China 

⁎Corresponding authors at: Beijing Municipal Key Laboratory of Advanced Energy Materials and Technology, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.Beijing Municipal Key Laboratory of Advanced Energy Materials and TechnologySchool of Materials Science and EngineeringUniversity of Science and Technology BeijingBeijing100083China⁎⁎Corresponding author at: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences ＆ Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.Key Laboratory of Human Disease Comparative MedicineMinistry of HealthInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences ＆ Comparative Medical CenterPeking Union Medical CollegeBeijing100021China

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Highlights

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We identified pathways correlated with IL-1R8 expression in mouse splenocytes by gene expression microarrays.
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Cell migration-related genes downregulated in Il1r8−/− splenocytes were identified.
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IL-1R8-depleted RAW264.7 cells or Il1r8−/− BMDMs exhibited impaired cell migration.
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IL-1R8 is a new positive regulator for macrophage migration.
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IL-1R8 suppresses macrophage proliferation in a p38 MAPK-dependent manner.

Il testo completo di questo articolo è disponibile in PDF.

Abstract

IL-1R8, also known as the Single immunoglobin interleukin-1 (IL-1)-related receptor (Sigirr), has been demonstrated as a negative regulator of IL-1R and Toll-like receptor (TLR) downstream signaling pathways and inflammation. However, the role of IL-1R8 in macrophage migration and proliferation remains unknown. Here we investigated transcriptome profiles of WT and Il1r8-deficient splenocytes and found that innate immunity and cell migration related pathways were significantly correlated with IL-1R8 expression. Cell migration-related genes were downregulated in Il1r8−/− splenocytes or IL-1R8-depleted RAW264.7 cells. Further experiments revealed that IL-1R8-depleted RAW264.7 cells or Il1r8−/− BMDMs exhibited impaired cell migration. Moreover, we found that IL-1R8 suppresses macrophage proliferation through p38 MAPK signaling pathway. Therefore, our study suggests that IL-1R8 is a new positive regulator for macrophage migration and suppresses macrophage proliferation.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : IL-1R8, Transcriptomic analysis, Macrophage, Cell migration, Proliferation


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