TY  - JOUR
A1  - Schiffmann, Susanne
A1  - Gunne, Sandra
A1  - Bende, Marina
A1  - Ulshöfer, Thomas
A1  - Steinhilber, Dieter
A1  - Sethmann, Annette
A1  - Parnham, Michael J.
T1  - Sodium bituminosulfonate used to treat rosacea modulates generation of inflammatory mediators by primary human neutrophils
T2  - Journal of inflammation research
N2  - Background: Sodium bituminosulfonate is derived from naturally occurring sulphur-rich oil shale and is used for the treatment of the inflammatory skin disease rosacea. Major molecular players in the development of rosacea include the release of enzymes that process antimicrobial peptides which, together with reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF), promote pro-inflammatory processes and angiogenesis. The aim of this study was to address the molecular mechanism(s) underlying the therapeutic benefit of the formulation sodium bituminosulfonate dry substance (SBDS), which is indicated for the treatment of skin inflammation, including rosacea.
Methods: We investigated whether SBDS regulates the expression of cytokines, the release of the antimicrobial peptide LL-37, calcium mobilization, proteases (matrix metalloproteinase, elastase, kallikrein (KLK)5), VEGF or ROS in primary human neutrophils. In addition, activity assays with 5-lipoxygenase (5-LO) and recombinant human MMP9 and KLK5 were performed.
Results: We observed that SBDS reduces the release of the antimicrobial peptide LL-37, calcium, elastase, ROS and VEGF from neutrophils. Moreover, KLK5, the enzyme that converts cathelicidin to LL-37, and 5-LO that produces leukotriene (LT)A4, the precursor of LTB4, were both inhibited by SBDS with an IC50 of 7.6 μg/mL and 33 μg/mL, respectively.
Conclusion: Since LTB4 induces LL-37 which, in turn, promotes increased intracellular calcium levels and thereby, ROS/VEGF/elastase release, SBDS possibly regulates the LTB4/LL-37/calcium – ROS/VEGF/elastase axis by inhibiting 5-LO and KLK5. Additional direct effects on other pro-inflammatory pathways such as ROS generation cannot be ruled out. In summary, SBDS reduces the generation of inflammatory mediators from human neutrophils possibly accounting for its anti-inflammatory effects in rosacea.
KW  - sodium bituminosulfonate
KW  - rosacea
KW  - neutrophils
KW  - 5 lipoxygenase
KW  - KLK5
KW  - MMP9
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62940
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-629400
SN  - 1178-7031
N1  - This work was supported by the Landesoffensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz (LOEWE), Centre Translationale Medizin und Pharmakologie (TMP) and partially funded by ICHTHYOL-GESELLSCHAFT Cordes, Hermanni & Co. (GmbH & Co.) KG.
VL  - 14
SP  - 2569
EP  - 2582
PB  - Dove Medical Press
CY  - Albany, Auckland
ER  -