Lamp1 controls CXCL10-CXCR3 axis regulated macrophage polarization and autophagy

Abstract BackgroundHigh expression of CXCL10 and its receptor CXCR3 is a response in inflammatory tissues and cells. Macrophage polarization and autophagy play important roles in macrophage related inflammatory. The cellular function of CXCL10-CXCR3 axis in macrophages is not well addressed. In this report, we determined the roles of CXCL10-CXCR3 axis in macrophage polarization and autophagy. ResultsFirst CXCL10 promotes the expression of M2 polarization markers (Arg1, Mrc1, Mmp9, VEGFa) and decreases the expression of M1 markers (IL-1b, IL-6, TNFa). In contrast, CXCR3 antagonist AMG487 promotes the expression of M1 markers and inhibits that of M2 markers. Next, we found that activation of CXCR3 by CXCL10 promotes the expression of autophagy proteins (Atg5-Atg12 complex, p62, LC3-II, and Lamp1) and AMG487 inhibits their expression. Moreover, knockdown Lamp1 by siRNA not only inhibits CXCR3 activation induced autophagy, but also switches the CXCL10-CXCR3 from M2 polarization to M1 polarization. CXCR3 activation caused the JNK expression decreased, and JNK inhibitor SP600125 treatment potentiates the CXCR3 activation induced Lamp1 expression and M2 polarization. In conclusion, ConclusionsCXCL10-CXCR3 axis regulates the macrophage polarization and autophagy via the inhibitory JNK and Lamp1, and Lamp1 controls the switch of CXCR3 mediated M1/M2 polarization and acts as a linker between polarization and autophagy.