Stevenson Nigel J, Addley Mark R, Ryan Elizabeth J, Boyd Caroline R, Carroll Helen P, Paunovic Verica, Bursill Christina A, Miller Helen C, Channon Keith M, McClurg Angela E, Armstrong Marilyn A, Coulter Wilson A, Greaves David R, Johnston James A
Infection and Immunity, Cancer Research and Cell Biology, School of Biomedical Science, Queen's University of Belfast, Belfast, Northern Ireland.
J Leukoc Biol. 2009 Feb;85(2):289-97. doi: 10.1189/jlb.0708394. Epub 2008 Oct 29.
The chemokine eotaxin/CCL11 is an important mediator of leukocyte migration, but its effect on inflammatory cytokine signaling has not been explored. In this study, we find that CCL11 induces suppressor of cytokine signaling (SOCS)1 and SOCS3 expression in murine macrophages, human monocytes, and dendritic cells (DCs). We also discover that CCL11 inhibits GM-CSF-mediated STAT5 activation and IL-4-induced STAT6 activation in a range of hematopoietic cells. This blockade of cytokine signaling by CCL11 results in reduced differentiation and endocytic ability of DCs, implicating CCL11-induced SOCS as mediators of chemotactic inflammatory control. These findings demonstrate cross-talk between chemokine and cytokine responses, suggesting that myeloid cells tracking to the inflammatory site do not differentiate in the presence of this chemokine, revealing another role for SOCS in inflammatory regulation.
趋化因子嗜酸性粒细胞趋化因子/CCL11是白细胞迁移的重要介质，但其对炎性细胞因子信号传导的影响尚未得到研究。在本研究中，我们发现CCL11可诱导小鼠巨噬细胞、人单核细胞和树突状细胞（DC）中细胞因子信号传导抑制因子（SOCS）1和SOCS3的表达。我们还发现CCL11可抑制一系列造血细胞中GM-CSF介导的STAT5激活以及IL-4诱导的STAT6激活。CCL11对细胞因子信号传导的这种阻断作用导致DC的分化和内吞能力降低，这表明CCL11诱导的SOCS是趋化性炎症控制的介质。这些发现证明了趋化因子和细胞因子反应之间的相互作用，表明追踪至炎症部位的髓样细胞在这种趋化因子存在的情况下不会分化，揭示了SOCS在炎症调节中的另一个作用。
