Effect of Chronic Adrenocorticotropine Hormone Treatment on LPS-induced Slight Inflammation via Inhibiting Nuclear Translocation of Glucocorticoid-glucocorticoid Receptor Complex in Lung of Pig
Effect of Chronic Adrenocorticotropine Hormone Treatment on LPS-induced Slight Inflammation via Inhibiting Nuclear Translocation of Glucocorticoid-glucocorticoid Receptor Complex in Lung of Pig
Zhiyuan Sun1, 3, Xuhui Zhang2,*, Xian Li3, Yanping Huang3, Shiyan Sui3, Weifeng Liu3, Guochao Ni3, Xiaozhou Xu1, Jianbo Yang1, Xue Lian1 and Hui Jia1
ABSTRACT
The crosstalk between glucocorticoid (GC) and immune response is critical for the maintenance of homeostasis. However, it remains elusive whether chronic stress affects lipopolysaccharide (LPS) -induced inflammation via the crosstalk. Pigs were administered LPS injection with or without continuous adrenocorticotropine hormone (ACTH) pretreatment. Twenty-four 30-day-old Duroc × Landrace × Large White crossbred piglets (12 ± 0.5 kg) were randomly assigned to 4 treatments: control, LPS, ACTH, and ACTH+LPS groups. Each group consisted of 6 male piglets. All ACTH pigs and ACTH+LPS pigs were injected intramuscularly with ACTH (2.25 IU/kg body weight) for 7 consecutive injections at 6-h intervals. Then, LPS pigs and ACTH+LPS pigs were injected intramuscularly with LPS (15 μg/kg body weight). LPS upregulated levels of pulmonary IL-1β, IL-10, TLR2 gene mRNAs (P <0.01, P =0.006, P =0.04, respectively), and T-NOS, iNOS and cNOS proteins (P =0.002, P =0.028 and P =0.003, respectively) and increased serum tumor necrosis factor alpha (TNF-α) concentration (P <0.01), but ACTH treatment has no significant effect on them. Neither ACTH nor LPS treatment had any significant effect on levels of pulmonary SOD, CAT and MDA secretion, as well as expression of IL-6, TNF-α, IL-10, COX-2 and TLR4 mRNAs (P >0.05). Pulmonary cortisol level was inhibited by LPS (P =0.034), with a similar trend of inhibition by ACTH (P =0.062). Pretreatment with ACTH tended to downregulate total GR protein levels (P =0.084), and LPS tended to inhibit GR protein expression in the nucleus (P =0.088). Pulmonary expression level of Let-7i targeted TLR4 was significantly increased by ACTH treatment (P =0.013), but not with LPS. These results suggest that LPS may increase the expression of pulmonary TLR2 mRNA by inhibiting nuclear translocation of GC-GR, thus causing a slight inflammatory response in the lungs of pigs, which is not affected by chronic ACTH treatment.
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February 2022
Vol. 54, Iss. 1, Pages 1-501
