Ibuprofen modulates macrophage polarization by downregulating poly (ADP-ribose) polymerase 1

Ibuprofen, a non-steroidal drug, is well known for its anti-inflammatory activity. The effects of ibuprofen on the polarization of macrophages are still not clear. Herein, we used THP-1 monocyte-derived macrophages to find that ibuprofen has inhibitory effects on the polarization of both classically activated M1 macrophages and alternatively activated M2 macrophages by downregulating NF-κB and JAK/STAT signaling pathways. During M1 or M2 polarization, ibuprofen also downregulated the expression of poly (ADP-ribose) polymerase 1 (PARP1). Furthermore, knockdown of PARP1 by either small interfering RNA or PARP1 inhibitor PJ34 can exert inhibitory effects on the polarization of M1 and M2, and alter the immune response of macrophages to the infection of Mycobacterium tuberculosis H37Ra. The results demonstrate that PARP1 plays a regulatory role in the ibuprofen-modulated polarization of macrophage, revealing the interplay between the DNA repair response process and macrophage polarization.