Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of
Thomas H. Leung, Lillian F. Zhang, Jing Wang, Shoucheng Ning, Susan J. Knox, Seung K. Kim
Submitter: Niloufar Kavian | email@example.com
Authors: Amélie Servettaz, Philippe Guilpain, Frédéric Batteux
Hôpital Cochin, GH Paris-Centre
Published December 11, 2013
Hypochlorous acid (HOCl) is an oxidizer widely used as bleach. HOCl, produced in neutrophils through the myeloperoxydase-catalysed oxidation of chloride by hydrogen peroxide, is pivotal in the defence against bacteria (1). HOCl is rapidly transformed into hydroxyl radical (OH°), that can react with a large variety of proteins and nucleic acids. Hydroxyl radical is the most reactive and the strongest oxidant molecule of all reactive oxygen species (ROS).
Leung et al. have recently reported that HOCl inhibits the activation of NF-kB through the oxidation of IKK in cultured keratinocytes, and attenuates skin lesions in two mouse models of NF-kB-driven epidermal diseases (2). Furthermore, HOCl induces epidermal hyperplasia and keratinocyte proliferation in the skin of aged mice, thus suggesting that HOCl could be a therapeutic tool in such skin diseases.
Since HOCl is presented here as a potential therapeutic agent in skin diseases, it must be stressed that exposure of skin to HOCl can also be terribly hazardous. Indeed, we have shown in 2009 that daily injections of HOCl into the skin of mice can induce in six weeks almost all the clinical and biological features of systemic sclerosis (SSc) (3). Those mice develop an extensive skin and lung fibrosis with differentiation of fibroblasts into myofibroblasts that produce high amounts of collagen, express α-Smooth Muscle Actin and overproliferate exactly as observed in the skin and lungs of SSc patients (4-6) (See also, Figure 1). Mice also develop the vasculopathy observed in SSc, with increased levels of serum sVCAM and sE-selectin (6-8). The inflammatory and autoimmune process that develops in those mice leads to increased levels of splenic B cells, production of the SSc-specific anti-topoisomerase-1 antibodies, skin and lung infiltration by T cells, and increased exhaled NO as in patients with SSc (3, 8-10).
If the paper by Leung et al. reports the hyperproliferative effects of HOCl on keratinocytes and an increased epidermal thickness, it presents no data on fibroblasts or dermis. Although the two protocols differ by the route of administration (intradermal injection versus skin exposure), the duration and the concentration of HOCl, the dramatic effects on keratinocytes after only two weeks in the paper by Leung et al., along with the lack of data on dermal impact must prompt clinical investigators to be very cautious if they decide to try such protocol in humans as suggested by the authors.
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