No adverse ocular complications related to subconjunctival injection were observed

g of 125I-labeled EDN1 to EDNRB increases significantly 2 days after incubation with KITL. Similarly, we reported that a single exposure of NHMs with UVB stimulates expression of the KIT receptor, whose function was assessed by an increased phosphorylation following KITL stimulation. Thus, it is likely that in addition to the increased production of melanogenic cytokines by UVB-exposed keratinocytes, EDNRB also plays a coordinated role in UVB-induced pigmentation by augmenting EDN1/EDNRB signaling through the accentuated function of EDNRB. In support of this, in UVB-exposed human skin where pigmentation is being stimulated, there is a significantly up-regulated expression level of EDNRB mRNA. However, little is known about intracellular PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19710468 signaling mechanisms involved in the stimulation of EDNRB expression in UVB-exposed NHMs. Anti-pigmentation agents have been developed as a target for various redox-sensitive biomolecules, including tyrosine hydroxylase or intracellular signaling intermediates during the melanogenesis cascade. Compounds including phytochemical agents or botanical extracts are adequate candidates for this purpose due to their distinct anti-oxidant properties. In this study, we found that a French maritime PBE containing rich flavonoids including OPC distinctly abrogates the increased expression of EDNRB at the transcriptional and translational levels following UVB radiation even when treated post-irradiation. PBE has a distinct antioxidant activity stronger than vitamin C and vitamin E as measured by lipid peroxidation of bovine retinal Varlitinib web tissue. Additionally, PBE possesses a potent scavenging activity for peroxynitrite, superoxide and nitric oxide, which play a central role in inhibiting the generation of these ROS. Further, PBE up-regulates the reduced-glutathione/oxidized-glutathione ratio. Owing to these strong antioxidant properties, it was anticipated 9 / 17 UVB Stimulates Endothelin B Receptor via a MSK1 Pathway Fig 6. Effects of treatment with UVB and/or PBE on phosphorylation of MAPKs. The PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19711918 phosphorylation levels of p38, JNK and ERK1/2 in NHMs at 15 min after treatment with or without 60 mJ/cm2 UVB and/or 30 g/ml PBE. Expression levels were detected by specific antibodies to non-phospho and phospho MAPKs. Error bars represent S.D. from triplicate experiments. P<0.05 and P<0.01 against NHMs UVB-irradiated in the absence of PBE, respectively. doi:10.1371/journal.pone.0128678.g006 that PBE has a potential to inhibit pigmentation by preventing the autoxidation of melanin. Since PBE can behave as an antioxidant and a scavenger for ROS generated by UVB irradiation, its possible inhibitory effect on the increased expression of EDNRB could be accounted for by the depletion of generated ROS if treated pre-irradiation. However, our observation that post-irradiation treatment with PBE can also abrogate the increased EDNRB expression strongly suggests that PBE abrogates the up-regulation of EDNRB expression via an unknown novel signaling mechanism in a ROS depletion-independent manner because the ROS lifetime is very short , not sufficient to deplete the generated ROS when treated immediately after UVB radiation. UVB exposure of human keratinocytes was reported to activate NFB signaling by stimulating IKK kinase which phosphorylates IkB, causing NFBp65 to transduce toward translocation into the nucleus during the signaling pathway downstream of the preceding p38 or JNK activation. In contrast, UVB exposure of human melanocytes