Document Type
Article
Publication Date
12-4-2013
Publication Title
Plos One
Abstract
Background: Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL–6, and cyclooxygenase-2 (Cox-2) by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN) inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown. Methodology: Bone marrow-derived macrophages (BMMs) were generated from RNase L+/+and −/− mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC)-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays. Conclusions/Findings: Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2). Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF)-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.
Recommended Citation
Yi, Xin; Zeng, Chun; Liu, Hongli; Chen, Xiaoli; Zhang, Ping; Yun, Boo Seok; Jin, Ge; and Zhou, Aimin, "Lack of RNase L Attenuates Macrophage Functions" (2013). Chemistry Faculty Publications. 398.
https://engagedscholarship.csuohio.edu/scichem_facpub/398
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.1371/journal.pone.0081269
Version
Publisher's PDF
Volume
8
Issue
12
Comments
This work was supported by a grant from the National Institutes of Health (R15DK084460-01A2) to AZ.