Inhibitory effect of glycyrrhizin on the neutrophil‐dependent increase of R5 HIV replication in cultures of macrophages

Yoshida, Tsuyoshi; Kobayashi, Makiko; Li, Xiao‐Dong; Pollard, Richard B; Suzuki, Fujio

It has been described that polymorphonuclear neutrophils (PMNs) enhance the replication of CC‐chemokine receptor 5/macrophage‐tropic (R5) HIV in cultures of monocyte‐derived macrophages (MDMs). In this study, the inhibitory effect of glycyrrhizin (GL) on R5 HIV replication influenced by PMNs was investigated in MDM cultures. The replication of R5 HIV in MDMs was greatly enhanced when cells were co‐cultured with freshly isolated PMNs (syngeneic to MDMs). When GL was added to this culture, however, the viral replication enhanced by PMNs was completely inhibited. CCL2 and interleukin 10 (IL‐10) were produced in cultures of PMNs exposed to R5 HIV, and the replication of R5 HIV was greatly enhanced in MDM cultures supplemented with a mixture of recombinant CCL2 and IL‐10. However, CCL2 and IL‐10 were not produced by PMNs exposed to R5 HIV, when GL was added to the cultures. In the presence of GL, these soluble factors were not detected in co‐cultures of MDMs and PMNs exposed to R5 HIV. In addition, the replication of R5 HIV in MDMs stimulated with CCL2 and IL‐10 was not directly influenced by GL. These results indicated that GL suppresses the PMN‐dependent increase of R5 HIV replication in MDMs through inhibiting CCL2/IL‐10 production by PMNs stimulated with R5 HIV.