Syk promotes phagocytosis by inducing reactive oxygen species generation and suppressing SOCS1 in macrophage-mediated inflammatory responses. (8th October 2022)

• Record Type: Journal Article
• Authors: Yi, Young-Su; Kim, Han Gyung; Kim, Ji Hye; Yang, Woo Seok; Kim, Eunji; Park, Jae Gwang; Aziz, Nur; Parameswaran, Narayanan; Cho, Jae Youl
• Is Part Of: International journal of immunopathology and pharmacology. Volume 36(2022)
• Publication Date: 2022-10-08
• Subjects: Syk -- phagocytosis -- reactive oxygen species -- SOCS1 -- nitration -- inflammation; Immunopathology -- Periodicals; Pharmacology -- Periodicals; Inflammation -- Periodicals; 615.1
• DOI: 10.1177/03946320221133018
• Languages: English
• ISSNs: 0394-6320

Abstract

Objective: Inflammation, a vital innate immune response against infection and injury, is mediated by macrophages. Spleen tyrosine kinase (Syk) regulates inflammatory responses in macrophages; however, its role and underlying mechanisms are uncertain. Materials and Methods: In this study, overexpression and knockout (KO) cell preparations, phagocytosis analysis, confocal microscopy, reactive oxygen species (ROS) determination, mRNA analysis, and immunoprecipitation/western blotting analyses were used to investigate the role of Syk in phagocytosis and its underlying mechanisms in macrophages during inflammatory responses. Results: Syk inhibition by Syk KO, Syk-specific small interfering RNA (siSyk), and a selective Syk inhibitor (piceatannol) significantly reduced the phagocytic activity of RAW264.7 cells. Syk inhibition also decreased cytochrome c generation by inhibiting ROS-generating enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and ROS scavenging suppressed the phagocytic activity of RAW264.7 cells. LPS induced the tyrosine nitration (N-Tyr) of suppressor of cytokine signaling 1 (SOCS1) through Syk-induced ROS generation in RAW264.7 cells. On the other hand, ROS scavenging suppressed the N-Tyr of SOCS1 and phagocytosis. Moreover, SOCS1 overexpression decreased phagocytic activity, and SOCS1 inhibition increased the phagocytic activity of RAW264.7 cells. Conclusion: These results suggest that Syk plays a critical role in the phagocytic activity of macrophages by inducing ROS generation and suppressing SOCS1 through SOCS1 nitration during inflammatory responses.