Immunomodulatory and anti-apoptotic effects of heme oxygenase-1 in hypoxia stress of small yellow croaker (Larimichthys polyactis).

Abstract

To clarify whether heme oxygenase-1 (HO-1) plays an immunomodulatory and anti-apoptotic role in hypoxia stress of small yellow croaker. In this study, histological observation, biochemical detection, gene expression detection, gene interference and other methods were used to explore the effects of hypoxia stress on non-specific immunity and apoptosis of small yellow croaker and the changes of SYCF cell immunity, inflammation and apoptosis after interference with ho-1 at the individual and cell levels. The results showed that hypoxia stress resulted in a significant decrease in the height, width and muscle thickness of the intestinal villi of small yellow croaker, and the number of goblet cells decreased. Splenic red blood cell swelling, increased intercellular space. The activities of immune-related enzymes (SOD, ACP, AKP, LZM) and the relative expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17c, TNF-α) mRNA in spleen, intestine, serum and SYCF cells were significantly changed under hypoxia stress, indicating that hypoxia stress induced inflammatory response and activated the immune system in small yellow croaker. The L. polyactis ho-1 orthologue (Lpho-1) was cloned and showed elevated mRNA and protein expression in intestinal and spleen tissues and cells under hypoxia. siRNA knock-down of Lpho-1 in SYCF cells followed by hypoxia reduced non-specific immune enzyme activities, up-regulated pro-inflammatory cytokine expression, decreased cell viability and increased caspase-3/8/9 activities. These data indicate that LpHO-1 protects L. polyactis against hypoxia by modulating immune enzyme activities, suppressing cytokine release and inhibiting apoptosis.