| Interleukin 8(IL-8), known as CXC chemokines 8(CXCL8), makes an important contribution to the regulation of immune responses, through its effects on specific and nonspecific immune cells chemotaxis and activation, on physiological or pathological condition. In teleost, the function of IL-8 on peripheral blood lymphocytes, head kidney lymphocytes and neutrophil chemotaxis has been verified, but its mechanism is still unclear. In this paper, we studied the mechanism of IL-8 in teleost by the intracellular signaling pathway of IL-8 and its interaction with other pro-inflammatory factors. High purity of recombinant grass carp IL-8 protein(rgc IL-8) was obtained, by optimization of the recombinant expression system and purification conditions. When employing the rgc IL-8 to grass carp head kidney leucocytes(HKLs), we found that rgc IL-8 induced the gene expression of its own, IL-1β and TNF-α through MAPK and NF?B signaling pathways. To reveal the interaction between IL-8 and other cytokines, antibody neutralization experiment was performed. The results showed that endogenous IL-8 was partially involved in the regulation of IL-1β to its own; However, endogenous IL-1β was not involved in the regulation of IL-8 to IL-8 and IL-1β gene expression. Moreover, IL-8 induce the expression of inducible nitric oxide synthase(i NOS) gene and production of nitric oxide(NO) in HKLs.This study revealed grass carp IL-8 regulated the gene expression of pro-inflammatory cytokines through MAPK and NF?B signaling pathway. Our job on IL-8 and IL-1β interaction not only promoted us to have a better understanding of the mechanism of IL-8, but also uncovered a new field of its function. Besides, we firstly verified grass carp IL-8 induced the production of NO in HKLs, which enriched the functions of teleost IL-8. To sum up, this study not only improves the grass carp IL-8 immune function, but also provides a potential target for the immune control of diseases in grass carp. |
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