Adrenocorticotropine hormone attenuated lipopolysaccharide-induced inflammation in porcine adrenal gland
In modern farms animals are at high risks of infectious diseases due to environmental stress factors.The adrenal gland is the terminal organ of stress response.The crosstalk between adrenal endocrine stress and innate immune response is critical for the maintenance of immune homeostasis during inflammation.Thus,it's important to explore whether stresses play a pivotal role in lipopolysaccharide(LPS)-induced inflammatory response in porcine adrenal gland.Here we established a model that pigs were administered LPS with or without continuous ACTH pretreatment.30-day-old Duroc × Landrace × Large White crossbred piglets(12 ± 0.5 kg)were randomly assigned to 4 treatments: Vehicle,LPS,ACTH,and ACTH+LPS groups.Each group consisted of 6 male piglets.Pigs in ACTH and ACTH+LPS groups were injected intramuscularly with ACTH(2.25 IU/kg)for 7 consecutive injections at 6 h intervals.Then,Pigs in LPS and ACTH+LPS groups were injected intramuscularly with LPS(15 g/kg).The results showed that LPS challenge alone induced mRNA expressions of IL-1β,IL-6,TNF-α,IL-10,COX-2,TLR2,TLR 4,and GR(P < 0.05,P < 0.05,P < 0.05,P < 0.05,P < 0.05,P < 0.01,P < 0.05,and P < 0.05,respectively).It's also associated with an increasing tendency of IL-6 protein level in adrenal gland(P = 0.065).TLRs 1-10 were all expressed in adrenal tissue.ACTH pretreatment appeared to down-regulate LPS-induced expressions of TNF-α,COX-2 and TLR4 mRNA,and down-regulated TLR2 mRNA and IL-6 protein level significantly(P < 0.05).Lipopolysaccharide alone did not affect ssc-miR-146b expression level compared to that in vehicle group. However, ACTH pretreatment in combination with LPS significantly increased this micro-RNA expression (P < 0.05), which may contribute to the diminished TLR4 expression. The LPS challenge alone induced remarkable compensatory mitochondrial damages at the ultrastructural level, which was alleviated by ACTH pretreatment. Accordingly, ACTH pretreatment was able to block LPS-inducible up-regulation of systemic and local adrenal cortisol levels (P < 0.05). Taken together, these results suggest that LPS stimulated the release of cytokines by activating TLR2 and TLR4 pathways, which may act directly on the adrenal gland and eventually promote cortisol release. The ACTH pretreatment was able to rescue LPS-mediated TLR2 and TLR4 activation for ultimately restoring systemic and local cortisols to basal physiological levels.
Stress Toll-like receptor Glucocorticoid Lipopolysaccharide Adrenocorticotropine
Sun zhiyuan Zhu mengling Liu qingxin Wang huicong Song chunlei Liu haixia Jia hui Cai demin Ge guojun
Department of Animal Husbandry and Veterinary Medicine,Jiangsu Polytechnic College of Agriculture an Department of Biochemistry & Molecular Medicine,School of Medicine,UC Davis,Sacramento CA 95817,USA
国内会议
江苏扬州
英文
1-20
2019-04-01（万方平台首次上网日期，不代表论文的发表时间）