Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice.

INTRODUCTION: Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen-peptide administration on immune response are unclear. In the present study, we tested the effects of collagen-peptide ingestion on allergic response and the effects of collagen-derived oligopeptides on CD4+ T-cell differentiation. METHODS: BALB/c mice fed a collagen-peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4+ T cells were stimulated with anti-CD3 and anti-CD28 in the presence of collagen-derived oligopeptides, and the expression of IFN-γ, IL-4, and Foxp3 was analyzed. RESULTS: In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA-specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T-helper (Th) type 1 and regulatory T (Treg) cells. In vitro T-helper cell differentiation assays showed that Hyp-containing oligopeptides promoted Th1 differentiation by upregulating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3+ Treg cells in response to antigen stimulation in the presence of TGF-ß. CONCLUSIONS: Collagen-peptide ingestion suppresses allergic responses by skewing the balance of CD4+ T cells toward Th1 and Treg cells and seems to be a promising agent for preventing allergies and inflammatory diseases.

Collagen peptide ingestion alters lipid metabolism-related gene expression and the unfolded protein response in mouse liver.

Ingestion of collagen peptide (CP) elicits beneficial effects on the body, including improvement in blood lipid profiles, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of CP ingestion on the liver, which controls lipid metabolism in the body. Male BALB/cCrSlc mice were bred with the AIN-93M diet containing 14 % casein or the AIN-93M-based low-protein diet containing 10 % casein or a diet containing 6 % casein+4 % CP for 10 weeks (n 12/group). Total, free and esterified cholesterol levels in the blood decreased in the CP group. DNA microarray analysis of the liver revealed that expressions of genes related to lipid metabolic processes such as the PPAR signalling pathway and fatty acid metabolism increased in the CP group compared with the 10 % casein group. The expressions of several genes involved in steroid metabolic process, including Cyp7a1 and Cyp8b1, were decreased, despite being targets of transcriptional regulation by PPAR. These data suggest that lipid metabolism in the liver is altered by CP ingestion, and the decrease in blood cholesterol levels in the CP group is not due to enhancement of the steroid metabolic process. On the other hand, expressions of genes related to the unfolded protein response (UPR) significantly decreased at the mRNA level, suggesting that CP ingestion lowers endoplasmic reticulum stress. Indeed, protein levels of phosphorylated inositol-requiring enzyme 1 decreased after CP ingestion. Taken together, CP affects the broader pathways in the liver - not only lipid metabolism but also UPR.

Effects of collagen peptide ingestion on UV-B-induced skin damage.

The effect of daily ingestion of collagen peptide on the skin damage induced by repeated UV-B irradiation was examined. Ingestion of collagen peptide (0.2 g/kg/d) suppressed UV-B-induced decreases in skin hydration, hyperplasia of the epidermis, and decreases in soluble type I collagen. These results suggest that collagen peptide is beneficial as a dietary supplement to suppress UV-B-induced skin damage and photoaging.