Psoriasis Is Associated with Low Serum Levels of Hydrogen Sulfide, a Potential Anti-inflammatory Molecule

Psoriasis Is Associated with Low Serum Levels of Hydrogen Sulfide, a Potential Anti-inflammatory Molecule

AMMAR K.H. ALSHORAFA,¹ QING GUO,¹ FANQIN ZENG,¹ MINGCHUN CHEN,¹ GUOZHEN TAN,¹ ZENGQI TANG¹ and RUOFEI YIN¹

¹Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China

Psoriasis, characterized by circumscribed, red, thickened plaques with an overlying silver-white scale, is a common T-cell-mediated chronic inflammatory skin disease. Although hydrogen sulfide (H₂S) has been shown to be a signaling molecule with both pro- or anti-inflammatory effects, its relationship with psoriasis has not been elucidated. In the present study, 15 patients with chronic progressive psoriasis and 15 healthy volunteers were investigated. Serum H₂S levels in psoriasis patients were significantly lower than those of healthy controls (16.69 ± 5.47 μM vs. 34.5 ± 6.39 μM). In contrast, serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in psoriasis patients than healthy controls (22.88 ± 6.24 pg/ml vs. 12.07 ± 3.68 pg/ml; 61.47 ± 8.21 pg/ml vs. 31.54 ± 13.73 pg/ml; and 39.43 ± 8.56 pg/ml vs. 20.55 ± 6.45 pg/ml, respectively). The serum H₂S levels negatively correlated with clinical disease severity. Furthermore, treatment of HaCaT human keratinocytes with TNF-α increased the levels of nitric oxide (NO), IL-6 and IL-8 (32.21 ± 5.71 μM vs. 3.22 ± 0.98 μM; 203.96 ± 13.16 pg/ml vs. 13.57 ± 3.75 pg/ml; and 301.24 ± 30.17 pg/ml vs. 29.06 ± 10.91 pg/ml, respectively) in the culture media. Exogenous H₂S inhibited the TNF-α-mediated upregulation of NO, IL-6 and IL-8 in a dose-dependent manner. In addition, H₂S inhibited TNF-α-mediated activation of p38, extracellular-signal-regulated kinase and nuclear factor kappa B. In conclusion, H₂S may play a protective role in the pathogenesis of psoriasis. H₂S-releasing agents may be promising therapeutics for psoriasis.

keywords —— hydrogen sulfide; inflammatory cytokines; mitogen-activated protein kinases; nuclear factor kappa B; psoriasis

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Tohoku J. Exp. Med., 2012, 228, 325-332

Correspondence: Fanqin Zeng, Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 west Yanjiang Road, Guangzhou 510120, P.R. China.

e-mail: fanqinzeng65@126.com