关键词: E. coli Immunomodulatory function Inflammatory responses Porcine beta defensin 2 TLRs signaling pathway

Mesh : Animals beta-Defensins / metabolism genetics Escherichia coli Swine NF-kappa B / metabolism Cell Line Toll-Like Receptors / metabolism genetics MAP Kinase Signaling System / drug effects Inflammation Signal Transduction

来  源:   DOI:10.1186/s12917-024-04220-7   PDF(Pubmed)

Abstract:
BACKGROUND: Porcine beta defensin 2 (pBD2) is one of the porcine beta defensins that has antibacterial activity, and plays an important role in the immunomodulatory activity that protects cells from pathogens. It has been reported that pBD2 plays their immunomodulatory functions related to the TLR4-NF-κB signal pathways. However, it is not completely clear how pBD2 reduces the inflammatory response caused by pathogens.
RESULTS: In this study, the effect of pBD2 on the expression of genes in the TLRs signaling pathway was investigated after IPEC-J2 cells were challenged with E. coli. The results showed that pBD2 decreased the expression of IL-8 induced by E. coli (P < 0.05), and pBD2 significantly decreased the expression of TLR4, TLR5 and TLR7 (P < 0.05), as well as the key downstream genes p38 and JNK which activated by E. coli (P < 0.05). In addition, pBD2 inhibited the p-p65, p-p38 and p-JNK which were up-regulated by E. coli.
CONCLUSIONS: pBD2 could reduce the inflammatory response induced by E. coli perhaps by inhibiting the TLRs-TAK1-NF-κB/MAPK signaling pathway which was activated by E. coli in IPEC-J2 cells. Our study further reveals the immunomodulatory activity of recombinant pBD2 against E. coli, and provides insights into the molecular mechanisms that protect cells from E. coli infection.
摘要:
背景:猪β防御素2(pBD2)是具有抗菌活性的猪β防御素之一,并且在保护细胞免受病原体侵害的免疫调节活性中起着重要作用。据报道,pBD2发挥与TLR4-NF-κB信号通路相关的免疫调节功能。然而,目前尚不清楚pBD2如何降低病原体引起的炎症反应。
结果:在这项研究中,在用大肠杆菌攻击IPEC-J2细胞后,研究了pBD2对TLRs信号通路中基因表达的影响。结果表明,pBD2降低了大肠杆菌诱导的IL-8的表达(P<0.05),pBD2显著降低TLR4、TLR5和TLR7的表达(P<0.05),以及大肠杆菌激活的关键下游基因p38和JNK(P<0.05)。此外,pBD2抑制由大肠杆菌上调的p-p65、p-p38和p-JNK。
结论:pBD2可能通过抑制大肠杆菌在IPEC-J2细胞中激活的TLRs-TAK1-NF-κB/MAPK信号通路来减轻大肠杆菌诱导的炎症反应。我们的研究进一步揭示了重组pBD2对大肠杆菌的免疫调节活性,并提供了保护细胞免受大肠杆菌感染的分子机制的见解。
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