Regulatory Effect of SOCS on NF-κB Activity in Murine Monocytes/Macrophages

SH Park, KE Kim, HY Hwang, TY Kim - DNA and cell biology, 2003 - liebertpub.com
SH Park, KE Kim, HY Hwang, TY Kim
DNA and cell biology, 2003liebertpub.com
The suppressor of cytokine signaling (SOCS) group of proteins has been implicated in
regulation of various cytokine signaling and in a negative crosstalk between distinct
signaling pathways. Interleukin-10 (IL-10) and LPS were known to induce expression of
SOCS-3 in neutrophils and monocytes/macrophages. IL-10 was also reported to inhibit a
proinflammatory signal-induced NF-κ B activation in monocytes and peripheral T
lymphocytes. The effects of increased SOCS-3 expression upon IL-10 regulation of NF-κ B …
The suppressor of cytokine signaling (SOCS) group of proteins has been implicated in regulation of various cytokine signaling and in a negative crosstalk between distinct signaling pathways. Interleukin-10 (IL-10) and LPS were known to induce expression of SOCS-3 in neutrophils and monocytes/macrophages. IL-10 was also reported to inhibit a proinflammatory signal-induced NF-κB activation in monocytes and peripheral T lymphocytes. The effects of increased SOCS-3 expression upon IL-10 regulation of NF-κB activation have not yet been demonstrated. Here we examined the effects of SOCS-3 on NF-κB activity. SOCS-3 did not induce any alterations in NF-κB activity induced by LPS or TNF-α. However, it enhanced RelA-dependent κB promoter activity when cotransfected with RelA. Similar results were observed with SOCS-1. In contrast, SOCS-2 did not show any regulatory effects on RelA activity. Analysis of C-terminal truncation mutants of SOCS-1 and SOCS-3 demonstrated that the SOCS box and its N-terminal region, a less well-conserved linker region were important for SOCS-3 activation of RelA. In contrast, the SOCS box itself was critical for SOCS-1 to activate RelA. These results suggest that SOCS proteins can enhance the effects of NF-κB/Rel proteins, and therefore, further modulate immune and inflammatory responses.
Mary Ann Liebert