scholarly journals Lumenato protects normal human dermal fibroblasts from neutrophil-induced collagen-3 damage in co-cultures

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248183
Author(s):  
Yulia Solomonov ◽  
Nurit Hadad ◽  
Oleg Pikovsky ◽  
Rachel Levy

Collagen is the major structural protein in the extracellular matrix of skin produced by fibroblasts. UV exposure results in infiltration of neutrophils within the epidermis and dermis, inducing collagen damage and contributing to the process of photo-aging. Collagen-3 is an integral structural component with collagen-1, and is an important regulator of collagen-1 fibrillogenesis. Addition of neutrophils activated with TNFα to normal human dermal fibroblast cultures, but not their supernatant, caused significant collagen-3 damage. To study whether Lumenato can protect from collagen-3 damage, it was added to co-cultures of Normal human dermal fibroblasts and neutrophils activated with TNFα. Lumenato prevented collagen-3 damage induced by activated neutrophils in a dose-dependent manner in the co-cultures. Lumenato also induced a low rate of collagen-3 synthesis in a dose-dependent manner detected by pro-collagen-3 secretion, but did not affect fibroblast cell number. Although Lumenato inhibited MMP-8, MMP-9, and elastase secreted from neutrophils, its main effect was in inhibiting both NADPH oxidase-producing superoxides and MPO activity-producing halides in a dose-dependent manner that correlated with protection from collagen-3 damage. In conclusion, the results suggest that Lumenato induces low levels of collagen-3 that may contribute for skin health and is very effective in defending the co-cultures from collagen-3 damage by inhibiting free radicals secreted from neutrophils, thus, indicating Lumenato's possible potential for skin protection.

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1156
Author(s):  
Madelaine Sugasti-Salazar ◽  
Yessica Y. Llamas-González ◽  
Dalkiria Campos ◽  
José González-Santamaría

Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.


2016 ◽  
Vol 81 (2) ◽  
pp. 376-379 ◽  
Author(s):  
Eriko Uehara ◽  
Hideki Hokazono ◽  
Takako Sasaki ◽  
Hidekatsu Yoshioka ◽  
Noritaka Matsuo

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Serban Iren Andreea ◽  
Costache Marieta ◽  
Dinischiotu Anca

In the dermis, fibroblasts play an important role in the turnover of the dermal extracellular matrix. Collagen I and III, the most important dermal proteins of the extracellular matrix, are progressively altered during ageing and diabetes. For mimicking diabetic conditions, the cultured human dermal fibroblasts were incubated with increasing amounts of AGE-modified BSA andD-glucose for 24 hours. The expression of procollagenα2(I) and procollagenα1(III) mRNA was analyzed by quantitative real-time PCR. Our data revealed that the treatment of fibroblasts with AGE-modified BSA upregulated the expression of procollagenα2(I) and procollagenα1(III) mRNA in a dose-dependent manner. High glucose levels mildly induced a profibrogenic pattern, increasing the procollagenα2(I) mRNA expression whereas there was a downregulation tendency of procollagenα1(III) mRNA.


Cosmetics ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. 36
Author(s):  
Young Joo Kim ◽  
Hwa Jun Cha

Inonotus obliquus, which is parasitic on birch and other trees, is a fungus in the family Hymenochaetaceae. In this study, we investigated whether Inonotus obliquus extracts used in traditional medicine were decreased in the expression of matrix metalloproteinases-1 (MMP-1) in the normal human dermal fibroblasts. As shown in our results, extracts of Inonotus obliquus decreased MMP1 expression in oxidative stress-exposed normal human dermal fibroblasts. Additionally, Inonotus obliquus extracts decreased AP-1 transcriptional activity and phospho-JNK in oxidative stress-exposed normal human dermal fibroblasts. Oxidative stress mediated the elevation of MMP1 mRNA expression and was well regulated by the JNK-AP-1 axis. Therefore, the results suggest that Inonotus obliquus extracts decreased MMP1 mRNA expression by regulating JNK-AP-1 axis. Additionally, Inonotus obliquus extracts have the potential to reduce collagen destruction and the formation of wrinkles and to be used as a cosmetic ingredient.


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