Abstract
The skin is the largest organ in the body and one of its main functions is to protect the body from environmental and endogenous noxious conditions, such as injury, infection and inflammation. The inducible nitric oxide synthase (iNOS) has been implicated as a key component in the inflammatory response. In the present study, we assessed the role of iNOS in the skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice deficient in iNOS had reduced edema and cellular infiltration in the skin following topical TPA application. Moreover, the genetic blockage of iNOS signaling inhibited the TPA-induced ERK and p38 activation resulting in reduced COX-2 upregulation. Finally, immunohistochemical studies revealed that iNOS knockout mice exhibited marked inhibition of AP-1, CREB and NF-κB transcriptional factors activation. Together, these results indicate that TPA induces the activation of several iNOS-dependent intracellular signaling pathways that have a key role in the control of inflammatory response in the skin. Therefore, selective iNOS inhibitors may be potentially relevant tools for cutaneous skin disease drug development.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.