| First Author | Chelvarajan L | Year | 2007 |
| Journal | J Leukoc Biol | Volume | 82 |
| Issue | 2 | Pages | 403-16 |
| PubMed ID | 17495050 | Mgi Jnum | J:123516 |
| Mgi Id | MGI:3718760 | Doi | 10.1189/jlb.0107071 |
| Citation | Chelvarajan L, et al. (2007) Molecular mechanisms underlying anti-inflammatory phenotype of neonatal splenic macrophages. J Leukoc Biol 82(2):403-16 |
| abstractText | Neonatal humans and rodents are susceptible to infection with encapsulated bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines by splenic macrophages (MPhi) from neonates. In this study, we show that when stimulated with a variety of agonists to TLR2, -4, and -9, neonatal MPhi make less proinflammatory cytokines and more IL-10 than adult MPhi. IL-10 appears to have a role in the decreased proinflammatory cytokine production, as neonatal MPhi treated with anti-IL-10 receptor antibody or from IL-10(-/-) mice produced levels of proinflammatory cytokines at a level comparable with that produced by adult MPhi. A microarray analysis of RNA from resting and LPS-stimulated MPhi from neonatal and adult mice showed that expression of a large number of genes encoding cytokines, chemokines, and their receptors was decreased dramatically in the neonatal MPhi, although some cytokines, including IL-10 and IL-16, were enhanced. Several genes in the TLR signaling pathway leading to NF-kappaB activation were down-regulated, which may account for the decreased chemokine and cytokine synthesis. It is surprising that p38alpha MAPK, known to be required for TLR-induced cytokine secretion, was enhanced in the neonatal MPhi. Our studies with the p38 MAPK inhibitor SB203580 suggested that excess p38 MAPK activity can be inhibitory for TLR2-, -4-, and -9-induced production of proinflammatory cytokines but not IL-10. The anti-inflammatory phenotype of the neonatal Mphi may be unique to the developing organism, although it compromises the neonate's ability to respond to encapsulated bacteria. |
