| First Author | Yi X | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e81269 |
| PubMed ID | 24324683 | Mgi Jnum | J:211016 |
| Mgi Id | MGI:5573028 | Doi | 10.1371/journal.pone.0081269 |
| Citation | Yi X, et al. (2013) Lack of RNase L attenuates macrophage functions. PLoS One 8(12):e81269 |
| abstractText | 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-alpha (TNF-alpha), interleukin (IL)-1beta, 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)-beta, IL-1beta, 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. |
