In vitro tests to determine the effect of collagen peptides on skin cells (fibroblasts and keratinocytes) found that cells with the protein blocked interleukin (IL-1B, and IL-8) and tumour necrosis factor alpha (TNF-a) expression that could render the host susceptible to infection.
Collagen also increased the expression of transforming growth factor beta (TGF-B) and vascular endothelial growth factor (VEGF) that promote wound-healing and encouraged collagen synthesis in skin fibroblasts.
The study authors assert that “such findings are extremely relevant once the senescence increases the incidence of mostly bacterial infections in the elderly”.
Collagen has broad health benefits, such as wound healing and dental therapy, treatment of sarcopenia, bone defects, osteoarthritis, and rheumatoid arthritis - and is the main protein in skin (dermis).
As we get older, collagen synthesis changes, resulting in a complete loss of type I collagen, shorter and thicker type III fibres, and loss of skin humidity and elasticity, which increases the risk of infection.
Human skin is largely made up of fibroblast and keratinocyte cell types, where the former essentially repairs damaged tissue and the latter synthesizes keratin. In addition, both help regulate skin immune responses and release cytokines to establish pro-inflammatory responses, the authors explain.
“It was reported that cytokines play a key role in the initiation, severity, and duration of the inflammatory process of the skin. In addition, the central involvement of fibroblasts and keratinocytes in this process was demonstrated,” they say.
However, over-production of pro-inflammatory cytokines can exacerbate age-related skin problems. For example, IL-1B and IL-8 are associated with cell damage and death, TNF-alpha is involved in the pathophysiology of psoriasis and focal infections, and excessive IL-6 inhibits tissue healing.
“On the other hand, excessive levels of TGF-B result in an impaired wound-healing process characterized by the dysregulated aggregation of extracellular matrix components, triggering fibrotic scar formation,” they add.
In vitro samples
The researchers developed a protocol to investigate whether collagen peptides inhibit inflammation induced by LPS and induce collagen synthesis by skin fibroblasts.
Human fibroblasts and keratinocytes were acquired and cultivated in a humid atmosphere. In total, 24 samples (including controls) were seeded at a concentration of 5 x 104 cells/mL using the RPMI 1640 medium and 10% bovine foetal serum with a high amount of glucose.
Intervention samples contained different concentrations of collagen or LPS, and LPS to collagen ratios. Experiments were carried out in triplicate and repeated once. Hydrolysed collagen peptides were supplied by Brazilian firm, PeptPure, and LPS derived from Escherichia coli.
The three collagen doses (2.5 mg/mL, 5 mg/mL and 10 mg/mL) increased skin cell proliferation however the higher 10 mg dose was the only one to increase the expression of pro-collagen-1 alpha (precursor of type I collagen fibres) and reduce the LPS-induced inducible nitric oxide synthase (iNOS) inflammatory response in fibroblasts.
The authors note that collagen in any dose reduced iNOS expression in keratinocytes.
LPS consistently increased the expression of interleukin cytokines (IL-1b, IL-6, and IL-8) and TNF-a, while collagen inhibited their release. LPS plus collagen (5 mg and 10 mg) also increased TGFB expression and LPS combined with any collagen dose increased VEGF.
“It was demonstrated for the first time that hydrolysed collagen in LPS-stimulated cells resulted in increased VEGF expression in both skin fibroblasts and keratinocytes,” the authors write.
“Furthermore, a synergistic effect among the growth factors, such as TGF-B and VEGF, in accelerating the healing process was demonstrated.”
Nevertheless, a causal relationship between hydrolysed collagen-induced TGF-B and pro-collagen-1a was not established within the scope of the study. In addition, they conclude that further in vivo investigations are required to determine whether observed effects may result in improved vascularisation in wound healing processes.
Published online, November 23, 2022: http://doi.org/10.3390/nu14234975
‘Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes’
Authors: Maysa Alves Rodrigues Brandao-Rangel, Carlos Rocha Oliveira, Fabiana Regina da Silva Olímpio, Flavio Aimbire, José Roberto Mateus-Silva, Felipe Augusto Chaluppe and Rodolfo P. Vieira