SHP-1 negatively regulates LPS-induced M1 polarization, phagocytic activity, inflammation and oxidative stress in primary macrophages of Chinese tongue sole (Cynoglossus semilaevis)

Macrophages serve as the primary effector cells in antibacterial immunity in teleost, engaging in both innate and adaptive immune response. However, the specific role of SHP-1, a multi-functional protein tyrosine phosphatase, in teleost macrophages remains elusive. In this study, we first established a cellular immune model using lipopolysaccharide (LPS), a major pathogenic component of Gram-negative bacteria, and then we comprehensively elucidated the function of SHP-1 in primary macrophages derived from Chinese tongue sole. Our results demonstrated that overexpression of SHP-1 inhibited M1 polarization, phagocytosis, respiratory burst of primary macrophages, suppressing the generation of excessive reactive oxygen species (ROS), malondialdehyde (MDA), and proinflammatory cytokines (il-1β, il-6), but increasing the expression of superoxide dismutase (SOD) and anti-inflammatory cytokine (il-10). Whereas SHP-1 silencing (through siRNA or inhibitor) exerted completely opposite effects, further emphasizing its roles as a negative regulator. More in-depth, we revealed that SHP-1 suppressed the activation/transduction of the TLR5-MYD88-NFκB and JAK-STAT3 signal pathways, thereby mitigating the excessive immune reaction in macrophages of Chinese tongue sole. In summary, our findings systematically delineate the functions of SHP-1 and offer mechanistic insights into the management of oxidative stress/inflammation-related diseases, which will contribute to the sustainable development of aquaculture.