| First Author | Iribarren P | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 9 | Pages | 6100-6 |
| PubMed ID | 16237106 | Mgi Jnum | J:119383 |
| Mgi Id | MGI:3701924 | Doi | 10.4049/jimmunol.175.9.6100 |
| Citation | Iribarren P, et al. (2005) IL-4 inhibits the expression of mouse formyl peptide receptor 2, a receptor for amyloid beta1-42, in TNF-alpha-activated microglia. J Immunol 175(9):6100-6 |
| abstractText | Microglia are phagocytic cells in the CNS and actively participate in proinflammatory responses in neurodegenerative diseases. We have previously shown that TNF-alpha up-regulated the expression of formyl peptide receptor 2 (mFPR2) in mouse microglial cells, resulting in increased chemotactic responses of such cells to mFPR2 agonists, including amyloid beta1-42 (Abeta42), a critical pathogenic agent in Alzheimer's disease. In the present study, we found that IL-4, a Th2-type cytokine, markedly inhibited TNF-alpha-induced expression of mFPR2 in microglial cells by attenuating activation of ERK and p38 MAPK as well as NF-kappaB. The effect of IL-4 was not dependent on Stat6 but rather required the protein phosphatase 2A (PP2A) as demonstrated by the capacity of PP2A small interfering RNA to reverse the effect of IL-4 in TNF-alpha-activated microglia. Since both IL-4 and TNF-alpha are produced in the CNS under pathophysiological conditions, our results suggest that IL-4 may play an important role in the maintenance of CNS homeostasis by limiting microglial activation by proinflammatory stimulants. |
