Loss of Extracellular Superoxide Dismutase Induces Severe IL-23-Mediated Skin Inflammation in Mice

Abstract

Psoriasis is a common chronic and complex autoimmune inflammatory skin disorder. The histological characteristics of psoriasis are epidermal hyperplasia, mononuclear leukocyte infiltration into the dermis, and increased angiogenesis. However, the mechanisms involved in the pathogenesis of psoriasis remain unclear. Extracellular superoxide dismutase (EC-SOD) has antichemotactic activities. Because immune cell infiltration is seen in psoriatic lesions and psoriasis patients express low levels of EC-SOD, we hypothesized that the lack of EC-SOD induces more severe IL-23-mediated psoriasis-like skin inflammation. To test this hypothesis, we determined whether the loss of EC-SOD causes more severe IL-23-induced skin inflammation. Ear skin after IL-23 administration was thicker in EC-SOD knockout (KO) mice compared with wild-type mice. In addition, infiltration of CD4(+) T cells, macrophages, and dendritic cells (DCs) into IL-23 injection sites was more elevated in EC-SOD KO mice. The expression of proinflammatory cytokines and chemokines was also more elevated in EC-SOD KO mice, and EC-SOD KO DCs expressed a higher level of MHCII. Finally, EC-SOD transgenic mice showed much less severe IL-23-induced skin inflammation. Therefore, EC-SOD may inhibit IL-23-induced psoriasis-like inflammation through the inhibition of immune cell infiltration and immune responses. These results suggest that EC-SOD could be a possible candidate for management of psoriasis.

Phytosphingosine Derivatives Ameliorate Skin Inflammation by Inhibiting NF-κB and JAK/STAT Signaling in Keratincoytes and Mice

“…Topical application of TPA induces IL1a-mediated acute and chronic inflammation and hyperplasia in mouse skin (Lee et al, 1994). In addition, intradermal IL-23 injection into the ears of mice induces chronic inflammation (Zheng et al, 2007;Rizzo et al, 2011;Maddur et al, 2012;Kim et al, 2013;Lee et al, 2013). These stimuli induce inflammatory responses in the skin that increase dermal edematous swelling, erythema, leukocyte infiltration, epidermal hyperplasia, and proliferation of epidermal keratinocytes.…”

“…In addition to the TPA-induced acute inflammatory model, we assessed a chronic inflammatory model by intradermal injection of IL-23 into the ears of mice (Zheng et al, 2007;Rizzo et al, 2011;Maddur et al, 2012;Kim et al, 2013;Lee et al, 2013). Intradermal IL-23 injection into mouse ear skin induced psoriasiform dermatitis that leads to ear thickness, edematous swelling, vascular permeability, and epidermal cell proliferation.…”

“…Phosphate-buffered saline or recombinant mouse IL-23 (500 ng per 10 ml, eBioscience, San Diego, CA) was intradermally injected into C57BL/6 mouse ears, followed by topical application of compounds every other day for 14 days as described previously Lee et al, 2013). Ear thickness was measured 24 hours after final injection and the ears were collected for further experiments.…”

Reactive Oxygen Species in Psoriasis and Psoriasis Arthritis: Relevance to Human Disease

“…EC-SOD knockout mice develop severe IL-23-mediated skin inflammation. The infiltration of immune cells at IL-23 injection sites and the expression of proinflammatory cytokines and chemokines are more elevated in these mice [126]. Interestingly, the IQM-induced mouse model shows an aberrant antioxidant system, with increased levels of myeloperoxidase and oxidative stress but less SOD activity.…”

Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver

“…Second, it is possible that ecSOD activity could impact the integrity of the HA itself. It has been shown that ecSOD activity protects tissues during noninfectious inflammation in the lung (20)(21)(22)(31)(32)(33)(34)(35). However, whether ecSOD activity protects the ECM from degradation in the basal state or during infection-induced inflammation has not been thoroughly investigated.…”