title: Lack of RNase L attenuates macrophage functions.
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.
  
  
  METHODS
  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
  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.
authors: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, Ohio, United States of America.
authors: Xin
authors: X
authors: Yi
authors: Chun
authors: C
authors: Zeng
authors: Hongli
authors: H
authors: Liu
authors: Xiaoli
authors: X
authors: Chen
authors: Ping
authors: P
authors: Zhang
authors: Boo Seok
authors: BS
authors: Yun
authors: Ge
authors: G
authors: Jin
authors: Aimin
authors: A
authors: Zhou
mesh_terms: D000818:Animals; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004705:Endocytosis; D004722:Endoribonucleases / Q000172:deficiency / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease