Activation of the JNK/MAPK Signaling Pathway by TGF-β1 Enhances Neonatal Fc Receptor Expression and IgG Transcytosis.

Shaoju Qian,Xi Liu,Chenxi Li,Yuncai Xiao,Xiangchao Jia,Zili Li

doi:10.3390/microorganisms9040879

Abstract

The neonatal Fc receptor (FcRn) transports maternal immunoglobulin G (IgG) to the foetus or newborn and protects the IgG from degradation. FcRn is expressed in several porcine tissues and cell types and its expression levels are regulated by immune and inflammatory events. IPEC-J2 cells are porcine intestinal columnar epithelial cells that were isolated from neonatal piglet mid-jejunum. We hypothesized that transforming growth factor β1 (TGF-β1) upregulated pFcRn expression in IPEC-J2 cells. To test this hypothesis, we treated IPEC-J2 cells with TGF-β1 and demonstrated that porcine FcRn (pFcRn) expression was significantly increased. SP600125, a specific mitogen-activated protein kinase (MAPK) inhibitor, reduced TGF-β1-induced pFcRn expression in IPEC-J2 cells. We performed luciferase reporter assays and showed that the c-JUN sensitive region of the pFcRn promoter gene was located between positions −1215 and −140. The c-JUN sequence, in combination with the pFcRn promoter, regulated luciferase reporter activity in response to TGF-β1 stimulation. Chromatin immunoprecipitation confirmed that there were three c-JUN binding sites in the pFcRn promoter. Furthermore, in addition to increased pFcRn expression, TGF-β1 also enhanced IgG transcytosis in IPEC-J2 cells. In summary, our data showed that the modulation of JNK/MAPK signaling by TGF-β1 was sufficient to upregulate pFcRn expression.

Highlights

The neonatal Fc receptor (FcRn), the specific receptor for immunoglobulin G (IgG), has a similar structure to major histocompatibility complex class I-like biomolecules which consist of covalently linked α heavy and β2M light chains
Western blotweUpregulated evaluated porcine FcRn (pFcRn) the effect of transforming growth factor β1 (TGF-β1) on pFcRn ting results showed that the pFcRn expression levels were increased
IPEC-J2 cells treated with TGF-β1 (8 ng/mL) for 2 h and 4 h increased pFcRn protein excells treated with

Summary

Introduction

The neonatal Fc receptor (FcRn), the specific receptor for immunoglobulin G (IgG), has a similar structure to major histocompatibility complex class I-like biomolecules which consist of covalently linked α heavy and β2M light chains. FcRn is widely expressed on the surface of epithelial cells, macrophages, and dendritic cells [1]. FcRn is reported to prevent IgG and albumin degradation during the internalization by endothelial and hematopoietic cells, increasing their half-life [3,4,5]. FcRn is involved in the cross-presentation of the immune complexes formed by the IgGs and their antigens [6]. FcRn is reported to participate in immune surveillance, especially in antigen presentation, phagocytosis, and mucosal immunity [6,9,10,11,12,13]

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