Figure 7.

A model for Lcn2 role as a negative regulator in NFκB-STAT3 loop activation in macrophages. Upon LPS stimulation, NFκB is rapidly activated, leading to the secretion of a range of proand anti-inflammatory cytokines. Proinflammatory cytokines such as IL-6 and other molecules subsequently stimulate STAT3 phosphorylation which further activates NFκB, forming a feed-forward loop. During the inflammatory response, Lcn2 is also increasingly secreted and acts as a fine-tuning regulator of inflammation in an autocrin/paracrine fashion. Lcn2 breaks the NFκB-STAT3 loop to limit the magnitude of inflammatory response by inhibiting NFκB activation. In the absence of Lcn2, NFκB-STAT3 loop activation and inflammation persist stronger and longer.