Toll-like receptor-mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages
Article first published online: 7 DEC 2011
© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd
Volume 135, Issue 1, pages 40–50, January 2012
How to Cite
Deng, T., Zhang, Y., Chen, Q., Yan, K. and Han, D. (2012), Toll-like receptor-mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages. Immunology, 135: 40–50. doi: 10.1111/j.1365-2567.2011.03511.x
- Issue published online: 7 DEC 2011
- Article first published online: 7 DEC 2011
- Accepted manuscript online: 26 SEP 2011 11:15PM EST
- Received 30 May 2011; revised 16 September 2011; accepted 16 September 2011.
- protein S;
- TAM receptors;
- toll-like receptor
Activation of Toll-like receptors (TLRs) triggers rapid inflammatory cytokine production in various cell types. The exogenous product of growth-arrest-specific gene 6 (Gas6) and Protein S (ProS) inhibit the TLR-triggered inflammatory responses through the activation of Tyro3, Axl and Mer (TAM) receptors. However, regulation of the Gas6/ProS-TAM system remains largely unknown. In the current study, mouse macrophages are shown to constitutively express Gas6 and ProS, which synergistically suppress the basal and TLR-triggered production of inflammatory cytokines, including those of tumour necrosis factor-α, interleukin-6 and interleukin-1β, by the macrophages in an autocrine manner. Notably, TLR signalling markedly decreases Gas6 and ProS expression in macrophages through the activation of the nuclear factor-κB. Further, the down-regulation of Gas6 and ProS by TLR signalling facilitates the TLR-mediated inflammatory cytokine production in mouse macrophages. These results describe a self-regulatory mechanism of TLR signalling through the suppression of Gas6 and ProS expression.