TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis.
TNF-alpha is a key cytokine in innate immune responses and is increased in psoriatic lesions. TNF-alpha has many effects, ranging from inflammation to apoptosis. These effects are reviewed to better understand the role of TNF-alpha as it relates to the pathogenesis and treatment of psoriasis. TNF-alpha increases production of pro-inflammatory molecules (e.g. IL-1, IL-6, IL-8, NF-kappa B, vasoactive intestinal peptide) and adhesion molecules (e.g. intercellular adhesion molecule-1, P-selectin, E-selectin). TNF-alpha promotes apoptosis through binding to the TNF-receptor 1; however, psoriatic lesions are hyperproliferative despite an increase in TNF-alpha. This paradox is partially explained as NF-kappa B activation seems to inhibit TNF-alpha-induced apoptosis. The importance of TNF-alpha and apoptosis in psoriasis is shown through the review of clinical trials using anti-TNF-alpha immunobiologics (e.g. etanercept, infliximab) and apoptosis-inducing treatments that result in clinical improvement of the disease.
Victor
Frank C
FC
UMDNJ/RWJMS-Clinical Research Center, 51 French Street, P.O. Box 19, Acute Care Bldg. 3rd Floor, New Brunswick, New Jersey 08901-0019, USA.
Gottlieb
Alice B
AB
D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use
D014409:Tumor Necrosis Factor-alpha