Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation - PubMed (original) (raw)

Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation

Xiang Zhong et al. Cell Stress Chaperones. 2012 Jul.

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.

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Figures

Fig. 1

Fig. 1

Expression of Hsp70 in the jejunum and ileum of NBW piglets and IUGR piglets. Values are means±SEM, n = 5 per treatment. Mean differences between values for IUGR piglets and NBW piglets are indicated by *P < 0.05. P_treatment_P value for treatment, P_intestinal site_P value for intestinal site, P_tr×int_P value for interaction between treatment and intestinal site

Fig. 2

Fig. 2

Expression of the NF-κB p65 subunits in the jejunum and ileum of NBW piglets and IUGR piglets. Values are means±SEM, n = 5 per treatment. Mean differences between values for IUGR piglets and NBW piglets are indicated by *P < 0.05. P_treatment_P value for treatment, P_intestinal site_P value for intestinal site, P_tr×int_P value for interaction between treatment and intestinal site

Fig. 3

Fig. 3

Expression of FoxO3a in the jejunum and ileum of NBW piglets and IUGR piglets. Values are means±SEM, n = 5 per treatment. Mean differences between values for IUGR piglets and NBW piglets are indicated by *P < 0.05. P_treatment_P value for treatment, P_intestinal site_P value for intestinal site, P_tr×int_P value for interaction between treatment and intestinal site

Fig. 4

Fig. 4

Activity of IKK (a), concentrations of IκB (b), activity of NF-κB (c), and expression of FoxO3a (d) induced by LPS, heat shock, and siRNA-mediated Hsp70 gene silencing in IEC-6 cells. Values are means±SEM, n = 6 per treatment. Means without a common letter differ (P < 0.05)

Fig. 5

Fig. 5

Apoptosis induced by LPS, heat shock, and siRNA-mediated Hsp70 gene silencing in IEC-6 cells. Values are means±SEM, n = 6 per treatment. Means without a common letter differ (P < 0.05)

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