CXCL10, a conserved bactericidal chemokine, harbors an antibacterial α-helix and mediates pro-inflammatory and chemotactic activities via p-ERK and p-AKT signaling in large yellow croaker (Larimichthys crocea)

CXCL10 is a multifunctional chemokine known for its roles in inflammation, chemotaxis, and immune regulation across vertebrates. However, whether CXCL10 exerts evolutionarily conserved functions in teleosts and the structural basis underlying these activities remain poorly characterized. In the present study, we found that large yellow croaker (Larimichthys crocea) encodes an evolutionarily conserved CXCL10 (LcCXCL10), which is induced by pathogens and IFN-γ and exhibits both conserved pro-inflammatory and chemotactic activities. LcCXCL10 significantly upregulates the expression of pro-inflammatory cytokines IL-1β, TNF-α, and IL-8, and promotes the directed migration of head kidney cells in a concentration dependent manner. Mechanistically, LcCXCL10 rapidly induces phosphorylation of ERK and Akt, and functional dissection revealed that chemotaxis is driven cooperatively by p-ERK and p-AKT, whereas pro-inflammatory cytokine expression is positively regulated by p-ERK and negatively modulated by p-AKT. Beyond its immunomodulatory functions, LcCXCL10 also possesses conserved but relatively weak bactericidal activity. Structural analysis identified that LcCXCL10 contains a conserved cationic amphipathic α-helix, which displays substantially stronger and concentration dependent antimicrobial activity than the full length protein. These findings demonstrated that CXCL10 from a representative teleost species integrates conserved immunomodulatory and direct bactericidal functions, underscoring the evolutionary conservation of chemokine mediated immune mechanisms across vertebrates.