SOCS regulates cell cycle arrest in periodontopathic bacterium–infected macrophages

Objectives: Suppressor of cytokine signaling (SOCS) is well known to a negative regulator to cytokine and LPS stimulation through JAK-STAT signaling pathway. Previous our study indicated that infection of Aggregatibacter actinomycetemcomitans (A.a.) in macrophages induced G1 phase arrest in cell cycle. In the present study, we investigated the role of SOCS in the induction of cell cycle in A.a.-infected macrophages. Methods: We performed cell cycle analysis by using FACS. In addition, we measured the expression of cell cycle associated protein, p21, cyclin D and Rb by Western blotting. The gene expression was detected by Real-Time RT-PCR. For making knock down cells, siRNA was induced to macrophages by Nucleofector. Results: In SOCS3 overexpressed cells, G1 arrest in cell cycle was inhibited, not in SOCS1 overexprresed cells. Western blotting analysis showed that the expression of cell cycle associated protein, p21 and pRb, was decreased and the expression of cyclin D was stability in SOCS3 overexpreesed cells. In SOCS3 knock down cells, A.a. infection had no effect in the expression of p21. Conclusions: Our results showed that intrinsic SOCS3 and SOCS1 upregulated the expression of p21, however, overexpression of SOCS3 induced downregulation of p21 expression but not SOCS1 in infected macrophages, suggesting that SOCS3 remarkably regulates cell cycle arrest in A.a.-infected macrophages.