title: Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation.
abstract: Neonates with intrauterine growth retardation (IUGR) are susceptible to decreases in cellular immunity. In recent years, a growing body of evidence indicates that Hsp70 may serve as a danger signal to the innate immune system and promote receptor-mediated apoptosis. Using neonatal pigs with IUGR, we investigated immune function of pigs and expression of heat shock protein 70 (Hsp70), nuclear factor-kappa B (NF-κB), and forkhead box O 3a (FoxO3a) in the intestinal tract. Samples from the blood, duodenum, jejunum, and ileum of normal body weight (NBW) piglets and IUGR piglets were collected at day 7 after birth. Furthermore, to test whether Hsp70 is associated with regulation of NF-κB and FoxO3a, Hsp70 was silenced using small RNA interference (siRNA) in IEC-6 cells. Body and intestinal weights were lower in IUGR piglets than in NBW piglets (p < 0.05). Proliferation of peripheral blood lymphocytes was decreased (p < 0.05) in IUGR piglets. Cytokine concentrations (IFN-γ, IL-4, IL-10, IL-1, and IL-8) were lower in serum of IUGR piglets. The levels of IFN-γ and IL-10 were decreased (p < 0.05) in the ileum of IUGR piglets, but IL-4 was increased (p < 0.05). The expressions of Hsp70 and FoxO3a were increased, and NF-κB activity was downregulated in IUGR piglets (p < 0.05). Furthermore, siRNA-mediated Hsp70 downregulation increased NF-κB activity, inhibited expression of FoxO3a, and decreased cell apoptosis. In contrast, overexpression of Hsp70 inhibited NF-κB activation. In conclusion, IUGR impairs immune functions in neonatal pigs. An inefficient immunity in IUGR piglets is associated with overexpression of Hsp70, which impairs NF-κB signaling and upregulates FoxO3a expression.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhong
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuexin
authors.initials: X
authors.lastname: Huang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Mireguli
authors.initials: M
authors.lastname: Yimamu
authors.forename: Nasir
authors.initials: N
authors.lastname: Raiput
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002460:Cell Line; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005317:Fetal Growth Retardation / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007111:Immunity, Cellular / Q000276:immunology*; D015151:Immunoblotting; D008214:Lymphocytes / Q000166:cytology; D009929:Organ Size; D034421:Sus scrofa
chemical_list: D018840:HSP70 Heat-Shock Proteins