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Dexamethasone modulates expression of genes involved in the innate immune system, growth and stress and increases susceptibility to bacterial disease in Senegalese sole (Solea senegalensis Kaup, 1858)
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摘要
Cortisol, the main glucocorticoid in fish, undertakes pleiotropic biological effects in response to stressors to maintain homeostasis. It can exert several actions on the immune system, growth and cellular metabolism, establishing a fine-tune regulation stress response and cross-talk interactions with other regulatory pathways. In this study, we investigated a causal relationship between high levels of glucocorticoids and susceptibility to pathogens and modification of gene expression profiles in Senegalese sole. For this purpose, we carried out two experiments using post-metamorphic individuals (21 days after hatching) that were exposed to dexamethasone (DXM), a potent glucocorticoid, in order to mimic cortisol effects. We quantified transcript levels of a wide set of genes involved in innate immune system (g-type lysozyme and hepcidin (hamp1)), HPI axis (crf, crfbp, pomc伪, pomc尾, gr1 and gr2), HPT axis (tgb), cellular stress defense system (hsp70 and hsp90aa), GH/IGF axis (igf-I and igf-Ir) and the neuropeptide trh. Short-term exposure to 0.1, 1 and 10聽ppm DXM provoked a reduction of pomc尾 transcripts and an increase of crfbp mRNAs in a dose-dependent manner at 48 and 72聽h after treatment. Moreover, g-type lysozyme transcript levels decreased significantly at 72聽h whereas hamp1 mRNA levels increased at 48聽h after exposure. Long-term DXM treatment (10聽ppm DXM) affected negatively weight of soles (鈭?0%lower than controls). Moreover, reduced mRNA levels were observed for pomc尾 after 1 week and igf-I and hamp1 after 2 weeks. In contrast, crfbp and crf increased mRNA levels after 2 weeks. hsp70 exhibited a dual response increasing transcript levels at 1 week after treatment and reducing thereafter. No significant changes in gene expression were observed at any time during this study for tgb, trh, hsp90aa, pomc伪, gr1 and gr2. Finally, a challenge experiment using the pathogen Photobacterium damselae subsp piscicida confirmed earlier and higher mortalities in DXM-treated animals. Taken together, these data indicate that a prolonged exposure to DXM increases the susceptibility to pathogens and reduces growth. Moreover, DXM can trigger a wide cellular response modulating the expression of genes involved in the innate immune system, HPI and GH/IGF axes as well as cellular stress defense. These results are highly valuable to evaluate responses associated to aquaculture stressful conditions and discriminate specific glucocorticoid-mediated effects.

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