Abstract
Macrophage polarization is a process by which macrophage expresses various functional signatures in response to microenvironmental signals. Two types of macrophage polarization have been characterized as M1 (anti-tumor) and M2 (pro-tumor) phenotypes. Many malignant tumors are associated with an inflammatory infiltrate as part of the reactive stroma that consists mainly of macrophages (often called tumor-associated macrophages, TAMs), which in some instances, comprise up to 50% of the cell tumor mass. In addition, TAMs play a crucial role in promoting cancer cell growth and metastasis. Therefore, modulation of macrophage polarization could be a strategy for treating cancer.
Inflammasomes are a group of cytosolic protein complexes, classically consisting an NOD-like protein (NLR), the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1. Activation of inflammasome results in assembly of the inflammasome, caspase-1 activation as well as IL-1 beta and IL-18 secretion. A number of studies have reported that increased concentration of IL-1 beta protein in tumor tissues is associated with poor prognosis for cancer patients.
Corylin is a main compound isolated from whole plant, fruit and seed of Psoralea corylifolia L. Our previous study demonstrated that corylin inhibits the production of TNF-alpha, IL-6 and NO by macrophages through inhibiting the activities of MAPKs and NF-kappa B. In the present study, we will examine the effect of corylin in regulating NLRP3 inflammasome activation and macrophage differentiation. Our experimental results indicated that corylin inhibits the activation of NLRP3 inflammasome. We will further examine the effect of corylin on the polarization of macrophages.
