Immunoregulatory Effects of Porcine Plasma Protein Concentrates on Rat Intestinal Epithelial Cells and Splenocytes.

Cristina Hernández-Chirlaque,Carlos J Aranda,Fermín Sánchez De Medina,Olga Martínez-Augustin,Borja Ocón,Javier Polo

doi:10.3390/ani11030807

Abstract

Simple SummaryBlood contains proteins which have interest as products that may regulate immune function. For this reason some protein-based products are currently used as nutritional supplements for animals, for instance two porcine concentrates, spray dried serum (SDS), and an immunoglobulin concentrate (IC). These products have shown to protect against colonic inflammation in rodents. In the present study we characterize the ability of these products to modulate immune function in isolated cells, namely intestinal epithelial cells (IEC18 cells) and rat spleen cells. Our data indicate that both porcine protein concentrates indeed alter immune cell function, based on the secretion of the modulators known as cytokines. In intestinal epithelial IEC18 cells they promoted the secretion of GROα and MCP-1 cytokines. In spleen cells they mainly inhibited the production of TNF, a key proinflammatory cytokine. In addition, the IC product augmented the release of IL-10, an anti-inflammatory cytokine. Taken together, our data indicate that the immunomodulatory effects observed in vivo are consistent with the direct actions of the protein concentrates on epithelial cells, T lymphocytes, and monocytes.Serum protein concentrates have been shown to exert in vivo anti-inflammatory effects. Specific effects on different cell types and their mechanism of action remain unraveled. We aimed to characterize the immunomodulatory effect of two porcine plasma protein concentrates, spray dried serum (SDS) and an immunoglobulin concentrate (IC), currently used as animal nutritional supplements with established in vivo immunomodulatory properties. Cytokine production by the intestinal epithelial cell line IEC18 and by primary cultures of rat splenocytes was studied. The molecular pathways involved were explored with specific inhibitors and gene knockdown. Our results indicate that both products induced GROα and MCP-1 production in IEC18 cells by a MyD88/NF-κB-dependent mechanism. Inhibition of TNF production was observed in rat primary splenocyte cultures. The immunoglobulin concentrate induced IL-10 expression in primary splenocytes and lymphocytes. The effect on TNF was independent of IL-10 production or the stimulation of NF-kB, MAPKs, AKT, or RAGE. In conclusion, SDS and IC directly regulate intestinal and systemic immune response in murine intestinal epithelial cells and in T lymphocytes and monocytes.

Highlights

Protein products have interest for immunomodulation and the promotion of health beyond their nutritional properties, i.e., as functional foods or nutritional supplements.spray dried plasma (SDP) has been used as a dietary supplement to promote animal growth
Culturing IEC18 cells, an intestinal epithelial cell line, with immunoglobulin concentrate (IC) or spray dried serum (SDS) induced the production of the proinflammatory cytokines growth regulated oncogene α (GROα) and monocyte chemoattractant protein 1 (MCP-1) (Figure 1A,B, respectively)
Our results indicate that NF-κB is clearly involved in the observed effects since its inhibition abrogated GROα and MCP-1 responses (Figure 1C,D, respectively)

Summary

Introduction

Spray dried plasma (SDP) has been used as a dietary supplement to promote animal growth This approach has been reported to exert protection against rotavirus diarrhea in pigs [1]. Several of these concentrates from bovine or porcine origin have been shown to affect the host response in animal models of intestinal and lung inflammation [2,3,4,5,6,7,8]. In young and senescent animals challenged by Staphylococcus aureus enterotoxin B, dietary supplementation with functional proteins from SDP of porcine origin has been shown to modulate the intestinal barrier and defense mechanisms, thereby reducing the degree of gut-associated lymphoid tissue activation [2,8,9]. Simultaneous protection against lung and colon inflammation has been documented for porcine SDP [14]

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