Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes

Abstract

Collagen-based products are found in different pharmaceuticals, medicine, food, and cosmetics products for a wide variety of applications. However, its use to prevent or improve the health of skin is growing dizzyingly. Therefore, this study investigated whether collagen peptides could induce fibroblast and keratinocyte proliferation and activation beyond reducing an inflammatory response induced by lipopolysaccharide (LPS). Human skin fibroblasts (CCD-1072Sk) and human keratinocytes (hKT-nh-skp-KT0026) were seeded at a concentration of 5 × 104 cells/mL. LPS (10 ng/mL) and three doses of collagen peptides (2.5 mg/mL, 5 mg/mL, 10 mg/mL) were used. The readout parameters were cell proliferation; expression of inducible nitric oxide synthase (iNOS); expression of pro-collagen-1α by fibroblasts; and secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF) by both cell types. The results demonstrated that all doses of collagen supplementation induced increased proliferation of both human fibroblasts (p < 0.01) and human keratinocytes (p < 0.001), while only the dose of 10 mg/mL induced an increased expression of pro-collagen-1α by fibroblasts. Similarly, only the dose of 10 mg/mL reduced LPS-induced iNOS expression in fibroblasts (p < 0.05) and keratinocytes (p < 0.01). In addition, collagen supplementation reduced the LPS-induced IL-1β (p < 0.05), IL-6 (p < 0.001), IL-8 (p < 0.01), and TNF-α (p < 0.05), and increased the TGF-β and VEGF expression in fibroblasts. Furthermore, collagen supplementation reduced the LPS-induced IL-1β (p < 0.01), IL-6 (p < 0.01), IL-8 (p < 0.01), and TNF-α (p < 0.001), and increased the TGF-β (p < 0.05) and VEGF (p < 0.05) expression in keratinocytes. In conclusion, collagen peptides were found to induce fibroblast and keratinocyte proliferation and pro-collagen-1α expression, involving increased expression of TGF-β and VEGF, as well as the suppression of an inflammatory response induced by LPS.

Effects of Hydrolyzed Collagen as a Dietary Supplement on Fibroblast Activation: A Systematic Review

“…New findings also suggest that hydrolyzed collagen possesses properties to reduce inflammatory markers and fibroblast proliferation. This emerging research showing this relationship is justified by the mechanism of action in which collagens are formed by fibroblasts (Brandao-Rangel et al, 2022), supporting the notion that collagen appears to stimulate fibroblast proliferation. Animal studies and cell culture experiments corroborate with this rationale (Chotphruethipong, Sukketsiri, Aluko, Sae-Leaw, & Benjakul, 2021; Offengenden, Chakrabarti, & Wu, 2018).…”

“…Eleven studies were included in this review (Benjakul, Karnjanapratum, & Visessanguan, 2018; Brandao-Rangel et al, 2022; Chai et al, 2010; Chotphruethipong, Aluko, & Benjakul, 2019; Chotphruethipong et al, 2022; Chotphruethipong, Sukketsiri, Aluko, et al, 2021; Chotphruethipong, Sukketsiri, Battino, & Benjakul, 2021; Lin et al, 2020; Offengenden et al, 2018; Y. Wang, Zhang, Zhang, & Li, 2011; Wauquier et al, 2022) for the outcome of stimulation or proliferation of fibroblasts by the application or ingestion of hydrolyzed collagen supplements or collagen peptides.…”

Chitosan/Gelatin Scaffolds Loaded with Jatropha mollissima Extract as Potential Skin Tissue Engineering Materials

“…Gelatin, which is a product obtained from the thermal and chemical degradation of collagen, when placed in a physiological environment, undergoes enzymatic and hydrolysis degradation [ 83 , 84 , 85 ]. Its degradation products promote the proliferation of the cells associated with wound repair and skin regeneration, such as keratinocytes, in addition to being pro-angiogenic, which favors soft tissue repair [ 84 , 86 , 87 ].…”

The Ethyl Acetate Extract of Caulerpa microphysa Promotes Collagen Homeostasis and Inhibits Inflammation in the Skin

“…The chronic inflammatory condition in senescent skin accelerates collagen loss and skin thinning. Further, immune cells activated by inflammation or other stimulators produce proteases (e.g., MMPs), cytokines (e.g., IL-1β, IFN-α), growth factors (e.g., TGF-β), and ECM components (e.g., fibronectin) and then participate in the remodeling of ECM components [ 46 , 47 ]. On the other hand, collagen peptides were found to suppress the LPS-induced inflammation in fibroblasts and keratinocytes [ 47 ].…”

“…Further, immune cells activated by inflammation or other stimulators produce proteases (e.g., MMPs), cytokines (e.g., IL-1β, IFN-α), growth factors (e.g., TGF-β), and ECM components (e.g., fibronectin) and then participate in the remodeling of ECM components [ 46 , 47 ]. On the other hand, collagen peptides were found to suppress the LPS-induced inflammation in fibroblasts and keratinocytes [ 47 ]. The above experiments seem to imply that there is dynamic crosstalk between anti-inflammation and collagen stability in skin.…”