Namazi M R, Salmanpour R, Handjani F, Jowkar F.
Nitric oxide may directly induce the psoriatic disease process via suppression of Keratinocyte Apoptosis and induction of Keratinocyte hyperproliferation.
J Pak Assoc Derma Jan ;14(4):232-6.

Nitric oxide (NO) has been supposed to induce the psoriatic disease process indirectly through increase of release and also effects of substance P and calcitonin gene-related peptide. This paper discusses the potential direct roles of NO by induction of keratinocyte hyperproliferation and suppression of keratinocyte apoptosis. NO has been shown to exert a biphasic effect on keratinocytes based on its concentration: increasing proliferation and decreasing differentiation of keratinocytes at low concentrations but producing the reverse effects at high concentrations (³500mm). Therefore, NO, having a maximum concentration of about 0.01mm in the psoriatic lesions, more likely induces keratinocyte hyperproliferation rather than suppressing it. Low production of NO in psoriasis occurs in the face of high overexpression of inducible nitric oxide synthase (iNOS) mRNA and protein and may be due to a) overexpression of arginase 1, which regulates iNOS activity by competing for the common substrate L-arginine, b) overexpression of calcitonin gene-related peptide, which inhibits iNOS activity, c) NO`s regulatory effect on its own production by binding to heme which mediates iNOS dimerization, and d) NO`s inhibition of the release of nerve growth factor which in synergy with TNF-a induces iNOS. Noteworthy, neopterin and cutaneous polyamines, which are also overexpressed in the psoriatic lesions, contribute further to the low production of NO via suppression of the expression of iNOS gene. Based on the observations that psoriatic keratinocytes are resistant to the induction of apoptosis and that NO, at low concentrations, is capable of suppressing apoptosis, this author suggests the apoptosis -suppressant effect of NO as another potential role for NO in inducing the psoriatic disease process.

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